Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics. Severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, emerged as a zoonotic virus and was identified as the causative agent of COVID-19 in December 2019. SARS-CoV-2 is a Betacoronavirus belonging to the Sarbecovirus subgenus, like SARS-CoV. Coronaviruses have a positive-sense RNA genome of 26–32 kilobases. This genome encodes four structural proteins: Spike (S), Nucleocapsid (N), Envelope (E) and Membrane (M). The most important for protective immunity is the glycoprotein Spike, which forms a trimeric structure on the virus surface and comprises two subunits. Spike subunit 1 (S1) contains the receptor-binding domain (RBD) responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor on the host cell, while Spike subunit 2 (S2) permits the fusion of the viral and cellular membranes. Nucleocapsid plays an important role in transcription enhancement and viral assembly.The kinetics of the SARS-CoV-2 antibody response following infection or vaccination have been analyzed in detail, with numerous studies demonstrating that specific immunoglobulin antibodies  to SARS-CoV-2 antigens develop between 6–15 days following symptom onset or vaccination. Following an initial period of boosting, antibody levels wane rapidly within the first 3–6 months, followed by a transition to a more slowly waning phase . Long-teAffinity maturation is the biological mechanism by which activated B cells undergo rounds of somatic hypermutations in immunoglobin genes, followed by an iterative clonal selection in germinal centers, resulting in the production of antibodies with greater affinities to the antigens over time ,7. StrucIn addition to providing insight into the immunology of SARS-CoV-2 infection, the measurement of antibody responses can provide valuable epidemiological information through the implementation of seroprevalence surveys . In the In contrast to monoplex assays such as ELISA, multiplex serological assays can simultaneously measure antibodies to multiple antigens, allowing for more epidemiological information to be obtained from a single test. It has been demonstrated that multiplex assays can have higher accuracy than monoplex assays ,12; can The majority of public health applications of serological assays involve the measurement of IgG or IgM antibodies. However, due to the distinct kinetic profiles of antibody responses, there are some notable examples where measuring avidity provides important additional clinical or epidemiological information. Avidity assays can be used to distinguish recent HIV infections from older infections , to diagThe samples used in this study are summarized in In a study of vaccine-induced immune responses, 86 residents of nursing homes in Dublin, Ireland, were followed before and after receiving two doses of the Pfizer BNT162b2 vaccine . Samples® system, and the median fluorescence intensity (MFI) was used for analysis. A 5-parameter logistic curve was used to convert MFI to relative antibody units relative to the standard curve generated on the same plate to account for inter-assay variation.A previously described 9-plex bead-based assay was used for simultaneous detection of antibodies to 5 SARS-CoV-2 antigens and 4 seasonal coronaviruses  in 1 μL serum or plasma samples [® MAGPIX® system, and the median fluorescence intensity (MFI) was used for analysis. Avidity was only assayed for IgG.To study avidity, we used a single concentration of a chaotropic agent to destabilize antibodies bound to antigens and measured the proportion of antibodies that remained bound after treatment in order to obtain a relative measure of the total binding strength of antibodies. The protocol was optimized by comparing the effects and dynamic range of three chaotropic agents  on avidity measurements and testing their side effects on target antigens coupled to beads, incubation times and concentrations. Following assay optimization, a routine avidity assay was performed by treating serum samples at a single concentration of urea at 6M. The protocol for the avidity assay was similar to that of the serological assay with the inclusion of an additional step. After the incubation of beads with serum samples, the bead–Ab complexes were washed with assay buffer PBT (PBS-Tween20 0.05%-BSA 1%) and then incubated for 5 min with 100 μL of urea 6M diluted in water or water alone as a control. After 3 washing steps, 100 μL of anti-IgG secondary antibody conjugated to R-phycoerythrin (Jackson Immunoresearch) diluted at 1/100 was added for 15 min. After 3 final washes to remove unbound secondary antibodies, plates were read using a LuminexAll statistical analyses were performed with R version 4.0.5. Median fluorescence intensities (MFIs) were converted to relative antibody units (RAU) with a 5-parameter logistic curve relative to the standard curve generated on the same plate. The avidity index (AI) was calculated as the MFI of the sample treated with the chaotropic agent divided by the MFI without the chaotropic agent times 100. Linear regression was used to compare the difference between the means of the different groups of time since infection with SARS-CoV-2.To assess whether avidity is of additional value to antibody measurements in the estimation of time since previous SARS-CoV-2 infection, we predicted time since infection with antibody measurements only and with antibody measurements and avidity estimates. We developed two random forest regression models. For each random forest, the number of trees was set at 1000. For each tree, two-thirds of the observations were used. Predictions were derived from the average of samples’ estimates in the remaining one-third of the samples, the out-of-bag samples. Regressions were built in a step-wise manner. First, the antigen in the regression was selected based on the importance of that antigen, measured by the mean decrease in accuracy on the out-of-bag samples. Subsequently, all other variables were added one by one to the most important antigen in the regression. The antigen associated with the lowest residual sum of squares was kept in the model. This process was repeated until no further decrease in the lowest residual sum of squares was observed. The randomForest package was used to develop and evaluate the random Forest regression models .We evaluated SARS-CoV-2-specific antibody responses over time in healthcare workers and care home residents following PCR-confirmed SARS-CoV-2 infection or administration of Pfizer’s BNT162b2 vaccine . IgA dirAnalysis of the kinetics of the SARS-CoV-2 IgG antibody avidity response revealed a general pattern of increasing avidity over the monitored timeframe for both healthcare workers who were vaccinated or naturally infected (The clear temporal trends in antibody avidity demonstrate that there is a statistical signal for estimating time since previous infection. Estimation of time since infection was conducted with two random forest regression models. In the first model, we considered IgG and IgA antibodies. In the second model, we also included avidity measurements. The regression model without avidity estimates showed that RAU to NP IgA provided the highest accuracy, followed by NP IgG and RBD IgA . The finCOVID-19 remains a critical threat to public health, and a deeper understanding of how antibodies are produced during infection is crucial. As can be seen from our results and others ,24,25, aPlasmodium falciparum malaria [Streptococcus pneumonia [The rationale is that for an equivalent number of antibodies, avidity can make a difference in terms of the quality of the response. Similarly, declining levels of antibodies over time could be partly compensated by an increase in avidity, thus maintaining an equivalent or even superior protective efficacy compared to serum with high antibody titers with poor avidity. This phenomenon has been observed in studies of vaccines against other pathogens, such as  malaria  or Strepneumonia , where bIn accordance with other studies , we founIn addition to being a critical tool for understanding the determinants of clinical protection, serological data can also provide important epidemiological information. Antibody avidity assays can be useful for the diagnosis of recent infections, as previously demonstrated for other pathogens such as measles, CMV or HIV ,16,18. TOne concern in the current situation is the continuous emergence and spread of SARS-CoV-2 variants characterized by antigenic changes in the Spike protein. These mutations are associated with reduced susceptibility to infection- or vaccine-induced immunity. Impaired binding efficiency of IgG to mutant RBD epitopes and enhanced stability of the ACE2-RBD complex  induced Altogether, we provide further evidence that the integration of the IgG avidity parameter in the serological toolkit combined with epidemiological models can play a useful role in the response to the COVID-19 pandemic.


Investigating the functions and activities of genes requires proper annotation of the transcribed units. However, transcript assembly efforts have produced a surprisingly large variation in the number of transcripts, and especially so for noncoding transcripts. This heterogeneity in assembled transcript sets might be partially explained by sequencing depth. Here, we used real and simulated short-read sequencing data as well as long-read data to systematically investigate the impact of sequencing depths on the accuracy of assembled transcripts. We assembled and analyzed transcripts from 671 human short-read data sets and four long-read data sets. At the first level, there is a positive correlation between the number of reads and the number of recovered transcripts. However, the effect of the sequencing depth varied based on cell or tissue type, the type of read and the nature and expression levels of the transcripts. The detection of coding transcripts saturated rapidly with both short and long-reads, however, there was no sign of early saturation for noncoding transcripts at any sequencing depth. Increasing long-read sequencing depth specifically benefited transcripts containing transposable elements. Finally, we show how single-cell RNA-seq can be guided by transcripts assembled from bulk long-read samples, and demonstrate that noncoding transcripts are expressed at similar levels to coding transcripts but are expressed in fewer cells. This study highlights the impact of sequencing depth on transcript assembly.The online version contains supplementary material available at 10.1186/s12864-022-08717-z. The genomic era has brought about a deep understanding of genomes . The seqTranscripts can be generally divided into two classes based on protein-coding ability –16. WhilThe low expression, poor concordance between databases and abundance of TE-derived sequences in noncoding RNAs suggest that noncoding transcript assembly is more complicated. Therefore, it is likely that more reads are required to assemble noncoding transcripts, however the full influence of sequencing depth for short and long-reads has not been previously described. In this study, we retrieved 671 publicly available short-read bulk RNAs-seq datasets from a panel of cell types and tissues with various numbers of reads to investigate the impact of sequencing depth on the assembly of coding and noncoding transcripts. We further focused on 150 human pluripotent stem cell (hPSC) samples for which extensive bulk short-read and matching long-read and single cell-RNA-seq (scRNA-seq) data are available. We report that the relationship between the number of reads and the number of recovered transcripts varied based on cell or tissue type, the type of read considered and the nature and expression levels of the transcripts, with the noncoding transcripts consistently benefiting more from deeper sequencing. Overall, we find that sequencing read depth has a relatively minor impact on the detection of coding transcripts, but a major effect on the recovery of noncoding transcripts.The short-read data used in this study were from an in-house collection of publicly available data  was subsampled using SAMtools [Two high-depth hPSC samples with over 200 million reads each (SRR597895 and SRR597912) , were us bowtie2  alignmenSAMtools . IndepenTo understand the relationship between sequencing depth and transcript assembly, we assembled transcripts from 671 human samples with sequencing depths ranging from 165,322 to 236,275,714 reads  . There are widespread problems in metadata annotations of sequencing samples –33, hencWe investigated the effect of read depth on the number of transcripts retrieved in hPSCs. We confirmed the positive relationships between the read counts and all transcript count Figs. A, S2A, cn = 272,209) [We then set out to explore the sensitivity of the transcript assembly. We defined false positives as a transcript that matched to the unfiltered superset of hPSC transcripts 272,209) . We chec72,209 . Since the unfiltered transcript set likely contains many unreliable transcripts, we repeated the hPSC transcript assembly sensitivity analysis by focusing only on the unfiltered hPSC transcripts that are in GENCODE Fig. G. The paWe next checked if noncoding transcript assembly would reach a saturation at much deeper sequencing depth. However, the deepest hPSC sample in our dataset (SRR597895) had less than 240 million reads. Therefore, we checked the distribution of coding and noncoding transcripts in the unfiltered superset of hPSC transcripts obtained from the merging of all the 150 hPSC samples (with > 5.5 billion paired reads) and found that 47.14% were coding while 52.86% were noncoding. This suggests that noncoding transcripts would continue to benefit from higher depth but the benefit slowed down. We therefore merged the top two, four and six high-depth hPSC samples and assembled the transcripts from the merged samples. The results show that the numbers of coding transcripts were similar, but the noncoding transcripts continue to benefit more . The novel transcripts contained a higher percentage of noncoding transcripts Figure SD. Across.We next checked if the sensitivity of the transcript assembly is similar between novel and GENCODE transcripts. Across different read depths, the GENCODE annotated set consistently had higher sensitivity Fig. E, suggesNext, we investigated the impact of sequencing depth on transcript steady-state (expression) levels. First, we investigated the cumulative RNA levels in shallow-depth samples (10 million reads) and a high-depth sample (200 million reads). The assembly from 200 million reads reached saturation more quickly than the assemblies of 10 million reads Fig. J. For exRecent studies have demonstrated the advantages of long-read sequences over short-read sequences for genome and transcript assembly –39. We tBecause of the limited number of iPSC-sequenced long-read samples, we focused on only the deeper sequenced H9 cell line for the subsequent analyses. To assess the impact of long-read depth, H9 reads were randomly subsampled to 25% (four replicates), 50% (two replicates) and 75% (one replicate). Assemblies with a similar number of reads had similar numbers of transcripts Fig. B. We conTo investigate how long read data perform with respect to TE presence, we checked the proportion of TE-containing transcripts across the read depths. While the proportion of TE-containing transcripts remain fairly stable for coding transcripts, the proportion of TE-containing noncoding transcripts tend to increase across depths Fig. F. IntereWe also investigated the impact of transcript expression level on transcript assembly from long-read data. We ranked the transcripts by expression in the 25% and 75% samples. The analyses of cumulative expression show that the top 10% of the transcripts account for about 90% of RNAs in the 25% subsamples, and about 93% of the total RNAs in 75% subsamples Fig. I. The prUnlike bulk short and long-read samples, single cell RNA-seq (scRNA-seq) read coverage is typically too low for transcript assembly. In scRNA-seq reads tend to be heavily 3’ biased, the data is sparse and suffers from transcript dropout from individual cells, and analysis is generally gene-wise, rather than transcript-specific . HoweverIn short-read bulk samples, we established that coding transcripts tend to be expressed in more samples Figs. I and 3F We confirmed the positive correlations between the barcode tag counts and the numbers of transcripts with detectable expression for both coding Figure SE and nonFinally, we investigated the effect of sequencing depth of the assembly on the number of transcripts with detectable expression in scRNA-seq data. For the short-read transcript assembly, we compared the transcript assemblies from 10 and 200 million reads. In both coding Fig. E and nonPrevious studies have identified differences between coding and noncoding transcripts , 42, 43.Several factors affect the number and accuracy of assembled transcripts. As stated above, noncoding transcripts tend to benefit more from higher sequencing depths. A possible reason for the difficulty in assembling noncoding transcripts may be partially due to the presence of TEs or lower apparent expression levels in bulk RNA-seq samples , 17, 36.Additional file 1.Additional file 2.


Many countries have been severely affected by the COVID-19 pandemic, including Sweden, which has been in the spotlight regarding its policies and their impact on mortality and morbidity. Therefore, it is of high interest to measure the disease burden of COVID-19 in terms of disability-adjusted life years (DALYs). DALYs have two main components: the years of life lost through premature death (YLL) and the number of years lived with disability (YLD). This study aims to measure DALYs due to COVID-19 in Sweden.This study used data from the nationwide multi-register observational study SCIFI-PEARL (Swedish COVID-19 Investigation for Future Insights - a Population Epidemiology Approach using Register Linkage) covering the entire Swedish population. The methodology used in the modelling and calculation of DALYs was based on the Global Burden of Disease guidelines, using Sweden-specific life tables for estimated life expectancies.In Sweden, 152877 DALYs were lost to COVID-19 between March 2020 and October 2021, corresponding to 1447/ 100 000, 99,3% of which was attributed to YLL. DALYs loss occurred mainly among elderly groups with 66,78 % of DALYs being attributed to individuals above 70 years old. 57,6% of the lost DALYs occurred among men that lost more DALYs compared to females in all age groups.Similar to other countries, the burden of COVID-19 in Sweden is concentrated mainly among the elderly, which contributed to the highest DALY loss due to mortality. Yet, DALY loss remains lower for COVID-19 compared to other major non-communicable diseases such as cardiovascular diseases and neoplasms. The contribution of YLD was minimal. However, YLD due to post-Covid is not well understood and long-term disability is likely still underestimated.• The burden of COVID-19 was mainly due to premature mortality in the older age groups.• More research is needed especially on post-COVID disability to derive better estimates of YLD.


Enhanced patient-provider engagement can improve patient health outcomes in chronic conditions, including major depressive disorder (MDD).We evaluated the impact of a digitally enabled care mobile app, Pathway, designed to improve MDD patient-provider engagement. Patients used a mobile interface to assess treatment progress and share this information with primary care providers (PCPs).In this 52-week, real-world effectiveness and feasibility study conducted in primary care clinics, 40 patients with MDD who were recently prescribed antidepressant monotherapy were randomized to use a mobile app with usual care  or usual care alone . Patients in the app arm engaged with the app daily for 18 weeks; a report was generated at 6-week intervals and shared with the PCPs to facilitate shared treatment decision-making discussions. The patients discontinued the app at week 18 and were followed through year 1. Coprimary outcome measures, assessed via research visits, included change from baseline in the 13-item Patient Activation Measure (PAM-13) and 7-item Patient-Provider Engagement Scale scores at week 18. Additional outcome measures included depression severity  and cognitive symptoms (5-item Perceived Deficits Questionnaire–Depression).P=.65). At 52 weeks, differences in PAM-13 scores from baseline demonstrated significantly greater improvements in the app arm than in the usual care arm . Compared with baseline, PHQ-9 scores decreased in both the app arm and the usual care arm at 18 weeks  and 52 weeks . Improvements in 7-item Patient-Provider Engagement Scale and WHO-5 scores were observed in both arms at 18 weeks and were sustained through 52 weeks in the app arm. Improvements in WHO-5 scores at 52 weeks were significantly greater in the app arm than in the usual care arm .All 37 patients  who completed the 18-week follow-up period  had moderate to moderately severe depression. Improvements in PAM-13 and PHQ-9 scores were observed in both arms. Increases in PAM-13 scores from baseline to 18 weeks were numerically greater in the app arm than in the usual care arm (mean 10.5, SD 13.2 vs mean 8.8, SD 9.4; Patients with MDD will engage with a mobile app designed to track treatment and disease progression. PCPs will use the data generated as part of their assessment to inform clinical care. The study results suggest that an app-enabled clinical care pathway may enhance patient activation and benefit MDD management.ClinicalTrials.gov NCT03242213; https://clinicaltrials.gov/ct2/show/NCT03242213 Major depressive disorder (MDD) is among the most common mental health disorders in the United States, with a lifetime prevalence of up to 20% . AlthougEffective management of MDD in primary care requires a systematic approach to diagnosis, patient education, treatment, close follow-up, and a commitment to adjusting care or consulting with specialists when needed ,10. One One proposed strategy to increase patient engagement, improve patient-provider communication to facilitate MDD management, and improve patient outcomes in primary care is the use of mobile health apps and digital platforms ,14. To iThe development of any mobile health and information technology tool, including those supporting MDD management, may benefit from collaboration between industry, app developers, and the health care team representing large health care systems . ResearcThe primary objective of this study was to determine whether the addition of the Pathway mobile app to usual clinical care improves patient-provider engagement in the management of MDD over an 18-week period. The secondary objectives of the study were to evaluate the impact of the Pathway mobile app on changes in certain patient-reported outcomes, including self-reported clinical depression severity , cognitive dysfunction (via the 5-item Perceived Deficits Questionnaire–Depression [PDQ-D5]), quality of life , and patient satisfaction, as well as changes in medication and medication adherence. Additional retrospective assessments were also planned to evaluate the impact of the app on measures of health care use 1 year after enrollment.In this randomized controlled pilot study , we enrolled patients diagnosed with MDD who were receiving primary care services at Advocate Health Care, which is now part of AAH. The study took place between July 2017 and January 2019 and involved 4 study sites in suburban and urban settings within metropolitan Chicago, Illinois, including Advocate Medical Group–Huntley, Advocate Medical Group–Hometown Family Medicine, Family Medicine Center in Ravenswood, and Adult Medicine Center in Oak Lawn. On identifying a patient with MDD who met the criteria for study participation, the physician providing care for that patient introduced the study; a designated research study coordinator then explained the study and obtained informed consent. Patients were then randomized to receive either the Pathway mobile app along with usual care or usual care alone. Participating patients were randomized based on the results from a randomized study list created using serially generated random numbers obtained by the study staff using a random number generator. Patients in the mobile app arm were encouraged to engage with the mobile app daily for 18 weeks . At weekThe mobile app was specifically designed to enhance patient-provider engagement, promote shared decision-making, and support measurement-based care in the management of clinical depression. It also provided patients with a way to track changes in clinical depression severity, cognitive symptoms, quality of life, emotional well-being, and adherence to medications; set up medication reminders; and record side-effect experiences. App functions included PHQ-9 and PDQ-D5 assessments conducted every 2 weeks, daily assessments of depression using 2 questions from the PHQ-9 and 1 question from the PDQ-D5, daily assessments of emotional well-being using a visual analog measurement of global well-being on a scale of 0 to 100, and daily cognitive symptoms assessed using the Cognition Kit 2-back test, in which patients indicate whether the symbol  matches the symbol 2 items back . PatientThe single-phase study included 2 follow-up periods: the primary follow-up period and the long-term follow-up period. The primary follow-up period began with randomization and continued through week 18. The long-term follow-up period began after the final visit at week 18 and continued through the 1-year follow-up phone interview (34 weeks after the use of the mobile app was discontinued). At year 1, the results from the follow-up phone interview and extraction of data from patients’ electronic medical records (EMRs) were analyzed to evaluate the residual impact of the app on patient-reported outcomes and health care use.Patients were eligible to participate in the study if they were aged 18 to 70 years, were receiving primary care for MDD at AAH, used an iPhone version 5 or later or a smartphone with an Android operating system, and had an active cellular data plan or regular Wi-Fi access. Patients were also required to have a PHQ-9 score of >5 at baseline, indicating at least mild depression severity , and to Patients were excluded from the study if they had a diagnosis of a major psychiatric disorder other than MDD, were considered to be at imminent risk of hospitalization due to MDD, had been hospitalized due to MDD within 3 months, had a significant risk of suicide or had a previous suicide attempt within 6 months, or had a history of responding only to combination or augmentation therapy in their current depressive episode. Patients for whom the use of antidepressants was contraindicated were not eligible for the study.Eligible patients were randomized to usual care  or usual care plus the mobile app  for 18 weeks (unblinded for both participants and researchers). An in-person introduction to the app and instructional handouts were provided to the patients at the time of enrollment. Although the use of the mobile app was encouraged, it was not required. Patients assigned to usual care received regular care as needed from their PCP; no specific interventions were mandated. At the end of the long-term follow-up period (1 year), patient-reported outcome measures were collected via follow-up phone calls. Data on health care resource use and medication changes during the long-term follow-up period were collected from medical chart reviews. A quality control committee reviewed the data for adequate completion and integrity.Study coprimary, secondary, and exploratory outcomes were assessed at 18 weeks for each arm via in-person research visits and phone interviews. Coprimary outcomes included changes in the 13-item Patient Activation Measure (PAM-13) scale and 7-item Patient Provider Engagement Scale (PPES-7) between baseline and 18 weeks. The PAM-13 scale was developed and validated to assess patient engagement and confidence in self-management of the disease ,22. The The secondary outcomes included changes (between baseline and 18 weeks) in depression severity evaluated using the PHQ-9 measure , cognitiExploratory outcomes included medication and dose switches, defined as medication switches, dosage changes, medication add-ons, or discontinuations (assessed via retrospective chart review), and patient and provider satisfaction with the care and use of the app. Additional assessments were collected throughout the study in the app arm via app functions such as the PHQ-9, PDQ-D5, emotional well-being, and cognitive symptom assessments. In addition, information on patient satisfaction with the app and app use data were collected from the patients in the app arm.After the 18-week end-of-study visit, patients and providers were invited to participate in a remote, qualitative, semistructured interview using a digital tool to discuss sentiments on app features and future features. This qualitative tool allowed the interviewer to observe and talk to the patients as they looked at the app’s features on their own devices, record the interview, and capture time-stamped notes.At the end of the long-term follow-up phase of the study (at year 1), a phone interview was conducted (34 weeks after the use of the mobile app was discontinued) to assess patient-reported outcomes, including patient and provider engagement (using PAM-13 and PPES-7), quality of life (using WHO-5), and depressive symptoms (using PHQ-9). At this time, a retrospective analysis that compared health care use between the app arm and the usual care arm was also conducted. Data were collected on inpatient visits, including depression-related hospitalizations; emergency department (ED) visits; outpatient visits, including visits to PCPs, psychiatrists, behavioral therapy specialists, and other health care providers; and medication and dose switches. Spontaneously reported serious adverse events were also recorded during the study period.t test or Mann-Whitney U test. Changes in categorical variables were compared using Fisher exact test or Pearson chi-square test. Two-tailed tests using a significance threshold of P<.05 were performed.This was a pilot study, and thus no sample size estimation was conducted. A sample size of 20 patients per group was expected to be sufficient to provide initial information about the potential effects and benefits of the app and the feasibility of its real-world use to inform future larger-scale studies. Patients were included in the analysis based on treatment allocation, and an intent-to-treat analysis was used. As 18-week follow-up data were not available for 3 randomized patients, these patients were dropped from the analysis, and an intent-to-treat analysis (with the exclusion of missing data) was conducted on the remaining population. For the primary and long-term follow-up periods, between-group differences in changes in continuous variables were evaluated using the 2-tailed Student A retrospective comparison of health care use was conducted between patients in the usual care arm and those in the mobile app arm using medical record extraction. This comparison included data from the time of consent to 1 year after enrollment for each patient. Health care use was compared between groups for long-term differences at 1 year after each patient’s study enrollment, overall, by cause (depression-related or not) and by category . Sensitivity analysis was used to assess attrition bias among patients lost to follow-up in the long-term follow-up period; these outcomes were used to assess the generalizability of the 52-week results across the original study group. Statistical analysis was performed using SAS software .This study (#Y5000249) was approved by the Advocate Health Care Institutional Review Board.A total of 40 patients were enrolled, and of them, 37 (93%) completed the 18-week primary follow-up period  and were52-week completers) were also similar between the groups , no statistically significant differences were observed.The baseline characteristics of patients who completed 18 weeks of the study are shown in P=.65). Patient-provider engagement improved in both arms based on changes in PPES-7 (Table S2 in P=.27).At week 18, both arms exhibited an increase in patient activation based on the PAM-13 scores (Table S2 in P=.73). In addition, no significant differences in the rates of depression response or remission between groups were reported. Response, defined as a ≥50% decrease in the PHQ-9 score from baseline, was achieved in 56% (10/18) of the patients in the app arm and 58% (11/19) in the usual care arm. Remission, defined as a PHQ-9 score of ≤5, was achieved by 39% (7/18) in the app arm and 44% (8/18) in the usual care arm. Cognitive symptoms (PDQ-D5) and quality of life (WHO-5) improved in both the app arm and the usual care arm .Depression severity (as measured by the PHQ-9 score) decreased in both arms  of patients in the app arm and 0% (0/18) of patients in the usual care arm switched medications during the study. One serious adverse event  was reported in the app arm.All patients randomized to the app arm  completed at least one app assessment during the study period. A majority of patients  completed the PHQ-9 and PDQ-D5 assessments biweekly for at least 12 weeks. A total of 70% (14/20) of the app users completed the self-report of medication assessment daily for >100 days.Patient satisfaction in the app arm was high, as shown in the results of the patient satisfaction survey administered at 18 weeks (Table S3 in P=.04). The quality of life (WHO-5) improved in both arms , with a significantly greater improvement observed in the app arm . Depression severity (as measured by the PHQ-9 score) decreased in both arms at year 1 . The longitudinal patient-reported outcomes among patients who completed the 52-week trial are shown in Table S4 in At year 1, a significant increase in patient activation (PAM-13) was observed for patients in the app arm  had more outpatient clinic visits to any provider than those in the app arm , including visits to PCPs (59 visits vs 38 visits). At 1-year follow-up, 3 patients in each group had a medication change: 1 patient in the mobile app arm and 2 in the usual care arm switched medications; 1 patient in each group had a medication dose change; and 1 patient in the mobile app arm added a new medication to their regimen.The results of this pilot study suggest that the Pathway mobile app may facilitate the systematic use of measurement-based care in MDD management, which can enhance shared decision-making and patient-provider communication, with improved medication adherence and treatment outcomes . The smac) in the normal range [In this study, the mean PAM-13 scores suggested that patients in the app arm, on average, moved from PAM-13 level 3 (58.2) to level 4 (74.2) at the end of the primary follow-up period, whereas patients in the usual care group, on average, started and remained at level 3. A cross-sectional study of patients visiting a primary care clinic reported that every 10-point increase in the PAM-13 score was associated with a 1% reduction in the predicted probability of having an ED visit or being obese and a 1% increase in the predicted probability of having clinical indicators  was observed among the patients in the app arm. Patient-provider engagement also showed small improvements in both arms. These results suggest that a larger study is warranted to determine whether the use of the app is associated with a clinically meaningful improvement in the symptoms of depression or patient-provider engagement.P=.04) and quality of life  was observed for patients in the mobile app arm than in the usual care arm, indicating that the app was associated with a long-term impact on patient activation that was sustained for at least 34 weeks after the app was discontinued. Small improvements were observed in both treatment arms with regard to patient-provider engagement (PPES-7) from baseline to week 52. It is possible that the reported improvement at year 1 among patients who completed the 1-year trial may be influenced by attrition bias. However, patients who were lost to follow-up were similar in most baseline characteristics to those who completed the study although they did have higher PHQ-9 scores at baseline and were more likely to have received education beyond high school. The similarity between the populations that completed the study and those that were lost to follow-up suggests that the year 1 results may be generalizable to the original study population.At year 1, greater improvement in patient activation  was greater for patients in the usual care arm than for those in the app arm. These examples may suggest that the app, through improved patient-provider communication, allowed for a more rapid response to changes in patient status while reducing the burden of in-person office visits.Several systematic reviews and meta-analyses have shown that the use of digital mental health interventions such as apps can aid in the reduction of depressive symptoms, with larger effects seen in patients with more severe symptoms ,29. In aAlthough the app users used the app for only 18 weeks, the 34-week follow-up period enabled us to determine whether the benefits of the app were sustainable. The length of the follow-up period is unique in the field of mobile health research on MDD. In fact, a recent review of the effectiveness of apps targeting patients with MDD identified 18 studies evaluating their impact on depression , and nonTwo important strengths of our pilot study were its randomized controlled study design and the long-term 1-year follow-up period. Another strength was that the app was developed and piloted in collaboration with end users in the health care team and cocreated with patient end users. Research has demonstrated that the effectiveness of digital technology resources can depend on the extent to which end users are included as active participants in their design . MoreovePotential limitations of the study included its small sample size, which limited our ability to identify statistically significant differences between groups, and the relatively short duration of app use although we were able to maintain follow-up with nearly half of the study’s participants after they discontinued its use. In addition, although patients and providers generally expressed high satisfaction with the app and interest in its features, both groups received limited education on how to use the app or its associated reports. The provision of additional education about the functionality and reporting features of the app might help increase patient-provider engagement and lead to improvements in the overall management of MDD. Embedding the reporting feature into the EMR rather than it being a stand-alone report might also improve the ability of PCPs to make real-time decisions about treatment. Additional work on the Pathway platform informed by the results of this study will help integrate the digitally enabled MDD care pathway into the current AAH system by assessing process and workflow improvements, clinician-patient experiences, collaborative care model enhancements, EMR integration, and efficiencies with other platforms.Our study data and qualitative insights informed the design of a real-world, prospective, interventional study of the app currently underway at AAH, designed to test the scaling and integration of the Pathway platform, along with educational interventions, at multiple primary care sites . The goal of this study was to determine whether the use of the app can improve adherence to measurement-based care practices in primary care to help improve outcomes for patients with MDD.This pilot study demonstrated that patients with MDD will engage with a mobile app designed to track treatment and disease progression and that health care providers will use the data generated as part of their assessment to inform care. The study results demonstrate that it is feasible to conduct an innovative app intervention in this diverse patient population with moderate to moderately severe depression. Introducing a customized, cocreated patient app into the care pathway can provide both patients and clinicians with greater details and trend data related to the disease state outside the traditional in-person visit. Enhanced use of patient-reported data within real-world health care settings can help support measurement-based care practices by making patient self-reported data and summaries of the data easy to interpret and easy to access within existing EMR instances.Although the sample size was small for the long-term follow-up phase of the study, the results of this feasibility study suggest that this digitally enabled MDD clinical care pathway approach may support shared decision-making and help provide sustainable benefits over at least 1 year. The impact of the app on patient activation and MDD management will be further explored in a larger prospective study of its real-world use in patients with MDD.


The COVID-19 outbreak resulted in two respective social and economic lockdowns in Greece. According to international findings pressure and instability may lead to the sense of losing control over the situation, and in retrospect to the escalation of psychosomatic symptoms for the general population.The present study examines whether five socio-demographic variables are significant to the variance of psychosomatic symptoms of the Greek population between the two domestic lockdowns.192 participants, of whom 141 were females(73.4%) and 51 males(26.6%), provided their answers between October 5 and November 18, 2020 to the research team of the Psychiatric Unit of the General Public Hospital of Nikaia, ‘Ayios Panteleimon’, in Athens, Greece. The participants were asked about their (i)‘income’, (ii)‘occupation’, (iii)‘residence’, (iv)‘marital status’ and (v)‘education’. Psychosomatic symptoms were measured through the self-reported PSSQ-29 tool .Out of the five One-way Between-participants ANOVAs, none of the five socio-demographic variables showed any significant statistical difference in the level of psychosomatic symptoms.The study provides some evidence against the protective and harmful role of the socio-demographic variables in psychosomatic health. It is noteworthy, that the conditions were not similar with previous studies. It might be possible that the COVID-19 worked as a phenomenon of mass panic for the Greek sample, and thus no socio-demographic background was either protective or harmful. In conclusion, the present study clearly highlights that none of them had any significant effect to the variance of psychosomatic symptoms for the general population.No significant relationships.


The SARS-CoV-2 pandemic has demonstrated the need to create highly effective antivirals and vaccines against various RNA viruses, including SARS coronaviruses. This paper provides a short review of innovative strategies in the development of antivirals and vaccines against SARS coronaviruses, with a focus on antisense antivirals, oligonucleotide adjuvants in vaccines, and oligonucleotide vaccines. Well-developed viral genomic databases create new opportunities for the development of innovative vaccines and antivirals using a post-genomic platform. The most effective vaccines against SARS coronaviruses are those able to form highly effective memory cells for both humoral and cellular immunity. The most effective antivirals need to efficiently stop viral replication without side effects. Oligonucleotide antivirals and vaccines can resist the rapidly changing genomic sequences of SARS coronaviruses using conserved regions of their genomes to generate a long-term immune response. Oligonucleotides have been used as excellent adjuvants for decades, and increasing data show that oligonucleotides could serve as antisense antivirals and antigens in vaccine formulations, becoming a prospective tool for immune system tuning. Cell life, similar to the life cycle of viruses, is controlled by nucleic acids. Nevertheless, it is undeniable that proteins play a leading role in the creation of vaccines and as targets for the action of antiviral drugs. DNA and RNA remain overshadowed by proteins in antiviral development, mostly used by researchers as a matrix for the creation of proteins. However, nucleic acids are shown to be immunogens, which allow them to be used in vaccine formulations, and antisense nucleic acid sequences can act as blockers of virus gene expression. All these qualities endow them with the ability to prevent and treat various diseases, including diseases caused by SARS coronaviruses.The first antisense oligonucleotide used as an antiviral preparation was used against the Rous sarcoma virus in the 1970s by Paul Zamecnik and Mary Stephenson  and JensAn interim success for the development of antisense antivirals was the drug fomiversen (Vitravene) produced by ISIS Pharmaceuticals in 1998, the first modified antisense oligonucleotide with a phosphorothioate (PS) backbone approved by the FDA for the treatment of cytomegalovirus retinitis in immunocompromised HIV patients . FomiverIn theory, use of antisense DNA oligonucleotides during gene expression can disrupt transcription, splicing, and translation. They employ four main mechanisms of action in eukaryotic cells. The first mechanism is steric blocking of protein synthesis. The second mechanism is based on the action of RNase H, which mediates the degradation of the mRNA–antisense oligonucleotide complex. The third mechanism of action relies on the ability of antisense oligonucleotides to form a triple helix by binding to DNA strands, which leads to inhibition of transcription initiation. The fourth mechanism is associated with the formation of the antisense oligonucleotide–mRNA complex, which can affect splicing . Due to Coronaviruses are spherical, enveloped, positive-sense single-stranded RNA viruses . They beShi et al. (2005) were among the first scientists to develop and implement antisense oligonucleotides as antivirals against SARS coronaviruses. They found some good target sites for antisense downregulation of SARS-CoV gene expression. Their results indicated a sequence-specific downregulation effect of antisense PS oligonucleotides (20mer) in Vero E6 cells, and the authors found an effective range of concentrations in which the antisense oligonucleotides inhibited expression of the E, M, and N genes of SARS-CoV in a concentration-dependent manner .A radically new approach uses computer modelling, taking into account the avalanche of accumulated databases of SARS-CoV-2 genomic sequences from the current pandemic ,23,24. SHasan et al. (2021) conducted in vitro experiments on the human cell line Huh7.5.1 and reported a ~50% decrease in SARS-CoV-2 RNA yield in treated cells. They designed antisense oligonucleotides that targeted structurally conserved regions of SARS-CoV-2 RNA (ORF1 and N) that reduced the viral infection ratio by 50% in the human cell line Caco-2, which was derived from human colon carcinoma cells. Cells were transfected with antisense oligonucleotides using lipofectamine; the transfection mechanism involved the formation of cationic liposomes that enabled the internalization of anionic antisense oligonucleotides. Then, when in contact with the cell membrane, the liposomes created endosomes that entered the cell . An innoThe use of new approaches in biochemistry has helped to create modified antisense oligonucleotides with complex structures. Su et al. (2021) reported on the design and construction of chimeric oligonucleotides comprising a 2′-OMe-modified antisense oligonucleotide and 5′-phosphorylated 2′-5′ poly(A)4 (4A2-5) to degrade envelope and spike RNAs of SARS-CoV-2 . The oliAnother promising therapeutic strategy is by circular RNAs (circRNAs), a type of noncoding RNA that is present in all eukaryotes. Back-splicing of certain pre-mRNA exons give origin to circRNAs. Pfafenrot et al. (2021) systematically tested a series of antisense-circRNAs targeting the SARS-CoV-2 genome RNA, specifically its structurally conserved 5′-untranslated region. Functional assays revealed that specific segments of the SARS-CoV-2 5′-untranslated region could be efficiently accessed by specific antisense-circRNAs, resulting in a reduction in virus proliferation of up to 90% in cell culture, with a durability of at least 48 h. The authors showed that the activity of antisense-circRNA was surprisingly robust against point mutations in the target sequence .Using an appropriate delivery system is a critical aspect for effective clinical applications of antisense oligonucleotides in both therapeutic and prophylactic contexts. The delivery of naked or unprotected antisense sequences could potentially expose them to enzymatic degradation, resulting in several negative side effects including toxicity, instability, and reticuloendothelial system and kidney clearance. Therefore, it is essential to optimize specific nanocarriers for the delivery of these fragile molecules to their target site . VariousAlthough there is no specific antiviral treatment recommended for MERS-CoV, antisense oligonucleotides can downregulate gene expression in MERS-CoV in a manner similar to SARS-CoV and SARS-CoV-2 to reduce MERS-CoV replication in treated cells.Generally, antisense oligonucleotides are well-tailored to the fast microevolution of SARS coronaviruses and their genomes in databases may help create very conservative sequences with relevant nucleotide modifications to provide a long operational half-life .The last two decades have witnessed a revolution in our understanding of how the innate immune system captures micropathogens, which has provided huge opportunities to gain an understanding of the design and development of adjuvants , or ‘dirOne of the first studies on the use of CpG oligonucleotides was by Anna Bielinski et al. (1990), who investigated the regulation of gene expression using double-stranded phosphorothioate oligonucleotides on the human immunodeficiency virus. Modified oligonucleotides accumulated in cells more efficiently than unmodified double-stranded oligonucleotides and modulated gene expression in a specific way .A significant contribution to the use of CpG oligonucleotides was also made by Arthur Krieg et al. (1995). They showed that phosphorothioate CpG motifs caused more than 95% of all spleen B cells to enter the cell cycle. The obtained data suggested a possible evolutionary link between the immune defense based on microbial DNA recognition and the phenomenon of ‘CpG suppression’ in vertebrates .In vivo studies on mice with gene knockout and in vitro studies with a cell-based analysis of TLR9 (toll-like receptor 9) activation found that TLR9 is a cellular receptor, or pattern recognition receptor, for CpG oligonucleotides ,43,44. ISynthetic oligonucleotides are powerful immunostimulants that have been studied for their use in the treatment of tumors, allergies, and infectious diseases, and as a vaccine adjuvant in humans. The immunostimulating effects of CpG oligonucleotides as vaccine adjuvants and their antimicrobial functions in domestic animals and bony fish are also being investigated .Hui-Tsu Lin et al. (2021) confirmed that rS1-adjuvanted with fucoidan/trimethylchitosan nanoparticles are good nanocarriers and adjuvant candidates for intramuscularly administered CpG oligonucleotide-adjuvanted SARS-CoV-2 rS1 protein vaccine. In the murine model, the rS1/CpG/NP formulation increased the longevity and breadth of NT activity; Th1-biased responses were induced by the formulation of a broad-spectrum IgG response. According to the results of the study, the authors suggested that the rS1/CpG/NP formulation was a promising COVID-19 vaccine candidate . CurrentNanishi et al. (2022) found that an aluminum hydroxide and CpG adjuvant formulation (AH-CpG) produced an 80-fold increase in the anti-receptor binding domain, neutralizing antibody titers in both age groups compared with aluminum hydroxide alone and protecting aged mice from a SARS-CoV-2 challenge. The AH-CpG elicited neutralizing antibodies against both wild-type SARS-CoV-2 and the B.1.351 (Beta) variant at serum concentrations comparable to those induced by the licensed Pfizer-BioNTech BNT162b2 mRNA vaccine. The AH-CpG formulation induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and enhanced cytokine and chemokine production in human mononuclear cells of younger and older adults [Yuntao Zhang et al. (2022) found that both novel low-dose and high-dose adjuvanted inactivated SARS-CoV-2 vaccines with CpG and Alum induced high levels of specific IgG antibodies and neutralizing antibodies against SARS-CoV-2, and the continuous stability of high-level neutralizing antibody titers over time showed that it had good, long-lasting immunity properties. Moreover, the vaccine exhibited equal effectiveness against the Beta, Delta, and Omicron variants through two immunization doses in rats, demonstrating its immune spectral properties. Positive correlations have been shown between virus-specific IgG antibody titers and COVID-19 severity .Thus, CpG oligonucleotides are strong adjuvants making connections between innate and adaptive immune systems. Chemical synthesis of oligonucleotides  is curreFor the human population, COVID-19 is the third significant coronavirus infection to occur in the twenty-first century, following severe acute respiratory syndrome (SARS) in 2002–2003 and Middle East respiratory syndrome (MERS) in 2012. MERS is still ongoing, with a total of 2601 laboratory-confirmed cases of Middle East respiratory syndrome (MERS) reported globally and 935 associated deaths at a case-fatality ratio (CFR) of 36%, from April 2012 to November 2022. The majority of these cases were reported in Saudi Arabia, with 2194 cases and 854 related deaths (CFR: 39%) . While tScientists have collected sporadic but convincing data over the past decades on the possibility of using nucleic acids as an active immunogen ,69,70,71The sequence of bacterial DNA, which has the unmethylated cytosine-guanine dinucleotide CG at its core (CpG), activates the mammalian immune system to produce antibodies rather than the DNA backbone . As thisThe current generations of coronavirus vaccines all use entire proteins or protein fragments to stimulate an immune response. The idea of oligonucleotide vaccines was first proposed by Oberemok et al.  in the fThe capacity of “La-S-so” oligonucleotide vaccines to activate adaptive immunity and function as efficient immunogens capable of inducing a potent immune response are key to their efficacy. One of the most important questions is how the viral particle inside a virion is neutralized by antibodies made on the nucleic acid. Antibodies produced in response to the La-S-so vaccine will not be able to attack the mature viral particle, as the virion contains the nucleic acid inside. We assume that the human body contains antibodies that can enter human cells during viral infection and target particular fragments of nucleic acids in RNA viruses. Generally speaking, antibodies do not easily pass through intact cellular or subcellular membranes in living cells ; howeverAnother important question is whether dendritic cells are capable of presenting vaccine fragments containing the unique nucleic acid sequence of viruses. Dendritic cells are leukocytes that are obtained from bone marrow, and are another key to a strong immune response. These cells can migrate throughout the body, during which they are sparsely distributed. The specialization of these cells is in the uptake, transport, processing, and presentation of antigens to T cells ,80. In oIn a number of our experiments with SARS-CoV-2, a semi-natural vaccine of the La-S-so type was found to have a moderate immune response, expressed by formation of specific antibodies. In addition, studies of the La-S-so vaccine were conducted in humanized mice with the human ACE2 receptor. By day 30 of the experiment, it was shown that while all the vaccinated animals were alive and beginning to recover, all the control mice had died. The morphological parameters of the lung parenchyma in vaccinated animals were comparable to those of intact animals (under publication). We assume that these observed effects cannot be solely explained by the adjuvant role of oligonucleotides. Research has continued on the selection of doses (fine tuning to discover the most effective amount) and refinement of constructs such as ‘La-S-so’ to find those with the best immune response .Thus, studies have shown that oligonucleotide constructs have great potential in the fight against SARS coronaviruses. The genetic material of SARS coronaviruses can be a source for the creation of antisense antivirals, oligonucleotide adjuvants, and oligonucleotide vaccines , and eveThe greatest advantage of the use of nucleic acids in practical applications lies in the fact that they are universal molecules and effective managers of the functional processes of the cell. The discovery in the field of the practical uses of nucleic acids as active tools of influence on cells has revolutionized biology. While there are no available low-cost antiviral drugs based on nucleic acids yet, it is only a matter of time before such drugs are developed. This is a promising approach as nucleic acids are natural biopolymers with predictable safety and efficacy. There is also the possibility of creating targeted drugs not only for specific diseases, but also for specific people. Oligonucleotide vaccines and antiviral drugs based on oligonucleotides could create a new spiral in the evolution of drugs for the prevention and treatment of viral diseases, including those caused by SARS coronaviruses.


The coronavirus disease 2019 (COVID-19) pandemic poses challenges to paediatric and adolescent HIV treatment programme. Modelling exercises raised concerns over potential impact of disruptions.To describe the impact of the COVID-19 pandemic on viral load (VL) testing among infants, children and adolescents on antiretroviral treatment (ART) in Durban, South Africa.Routinely collected, aggregated data of monthly VL counts done on all those less than 19 years old from January 2018 to January 2022 was analysed. An interrupted time series analysis using a Prais-Winsten linear regression model, including terms for lockdowns and excess mortality determined VL trends.P = 0.039, and percentage VL suppression rates  across COVID and pre-COVID periods, showing no significant difference, P = 0.262. In the interrupted time series analysis, modelled monthly VL counts did not differ significantly by lockdown level  or excess mortality . A significant downward trend in VL testing over time, including during the pre-COVID-19 period , was identified.The unadjusted mean VL was 2166  and 2016 (CI: 241.9), Viral load suppression for children and adolescents were not negatively affected by COVID-19. A trend of decrease in VL testing predated COVID-19.Evidence presented that HIV VL testing and suppression rates in children and adolescents in a high burden setting were sustained through the COVID pandemic. These are affected by COVID-19 lockdown regulations and may lead to suboptimal treatment adherence and retention to care.13The redirection of HIV healthcare funding and other resources could result in an inability to adequately support PLHIV along the continuum of care. While the most important impact of the pandemic on HIV programmes is ART interruption, the effects on HIV prevention, testing services, self-management and treatment adherence are also significant.The long-term implications of COVID-19 on health outcomes in infants, children and adolescents with HIV remain unknown, and there remains a lack of long-term studies on this vulnerable population in low- and middle-income countries (LMIC).This study aims to describe the impact of the COVID-19 pandemic on VL testing among infants, children and adolescents on ART in the eThekwini district, KZN, SA.15This was a retrospective cohort study that reviewed the facility-level VL data of infants, children and adolescents on ART across all public sector ART clinics in the city of Durban (eThekwini district), KZN. Durban has an estimated 1.7 million PLHIV in KZN, with 48 037 children under 15 years documented to be on ART and an overall HIV prevalence of 27%.The study period included 26 months designated as the pre-COVID-19 period (01 January 2018 to 28 February 2020) and 23 months of the designated COVID-19 period (01 March 2019 to 31 January 2022).17 and these restrictions were applied nationwide. Level 5 lockdown prohibited non-essential movement and mandated closure of non-essential businesses, schools and services. Health workers were exempt from movement restrictions, including clinical staff and data capturers. Antiretroviral treatment is provided free of charge at all clinics in eThekwini, which remained open during the entire study period. Before and throughout these lockdown periods, there were no reports of ART stock-outs in the study clinics. In addition, despite increased demands on laboratory testing for COVID-19, HIV VL testing capacity remained high and guidelines on VL testing remained unchanged throughout the study period.South Africa implemented a level 5 lockdown (the most severe of the five designated lockdown levels) at midnight on 26 March 2020,18Data were collected from the National Health Laboratory Service (NHLS) electronic registers and Tier.Net (three interlinked electronic registers for TB and HIV), a database for the facility-based patient management system in eThekwini district. Data on the number of VL tests done per month at each clinic are routinely recorded in Tier.Net and reported by gender and age group. During collation of the data per facility, the data were de-duplicated using a combination of first name, surname, date of birth and gender. We collected data from children and adolescents up to and including 19 years of age for the study period. We used predefined periods related to the national lockdowns and COVID-19 waves determined by the National Institute for Communicable Diseases Unit (NICD). Anonymised facility-level data were aggregated into monthly counts of numbers of VL tests done in specific age groups: 0–12 months, 12–60 months, 60 months – 15 years and 15–19 years. We categorised the VL results into three groups: under 10 000 copies/mL, between 10 000 and 100 000 copies/mL and over 100 000 copies/mL. We used excess mortality data for eThekwini from the South African Medical Research Council report on weekly deaths in South Africa.We used descriptive statistics to summarise demographic data and numbers of VLs taken per month during the study period. We also calculated the mean VL tests per month before and during COVID-19. Because this does not consider pre-existing trends in VLs, we conducted interrupted time series analyses by fitting a Prais-Winsten linear regression model to account for autocorrelation. The model included a time variable, a continuous variable for excess mortality in eThekwini, a dummy variable for each SA lockdown level 1 to 5, and a dummy variable for December when clinical activities are generally much reduced due to SA national holidays. This approach considers pre-lockdown trends and allows estimation of the effect of COVID-19 restrictions through lockdowns and the impact of COVID-19 waves on healthcare. Because different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants caused different levels of morbidity and mortality, we used excess mortality as a proxy for the impact of COVID-19 epidemic waves on the healthcare system. We conducted a sensitivity analysis with a negative lag of one month for excess mortality to account for the delays between SARS-CoV-2 infection, illness, hospitalisation and death. We used a separate dummy variable for each lockdown level to determine whether only a certain lockdown level affected VL numbers. We also built separate models for each age group. We analysed data using R 4.2 .This work was approved by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC/00003541/2021), the KwaZulu-Natal Department of Health’s Provincial Health Research Ethics Committee (KZ_202111_016), the eThekwini Municipality Health Unit, and the eThekwini District Health Department, with a waiver for informed consent for analysis of anonymised, routinely collected data.During the study period that extended from 01 January 2018 to 31 January 2022, a total of 102 624 VL tests were done on all patients 19 years and younger across all clinics in the eThekwini district. Of these, 2293 (2%) were from infants under one year of age, 8089 (8%) from children between one and five years, 52 704 (51%) from children between five and 15 years and 39 538 (39%) in those aged 15 to 19 years.Across all age groups, the mean number of VLs done per month was 2095 . Of all the VLs done in the study period, 73% were below 1000 copies/mL, indicating viral suppression. The percentage of patients virologically suppressed by age group was 66%, 63%, 76% and 73% for children below 1 year, 1–5 years, 5–15 years and 15–19 years. There was no significant difference in the percentage of virologically suppressed patients when we compared the pre-COVID-19 to the COVID-19 periods.In the linear regression model of numbers of monthly VLs taken among all patients 19 years old and younger that considers pre-COVID-19 trends, there was strong evidence that fewer VLs were done in December than in other months  .Although there was some suggestion that the number of VLs done reduced during level 5 lockdown and level 4 lockdown, neither of these effects was statistically significant. Of note, there was a large increase in VLs in the month before the level 5 lockdown, which may have offset the impact of the level 5 lockdown.Overall, there was evidence of a gradual decrease in the number of VLs taken over time (a decrease of six VLs per month). This trend was apparent in both the pre-COVID-19 and the COVID-19 periods.There was no evidence of an impact of COVID-19 variants  during various waves , includiIn analyses stratified by age , there wThis study reports on a large cohort of children and adolescents in HIV care in KZN spanning four years. We found that while the COVID-19 pandemic had no marked impact on VL testing and suppression rates, there were significant decreases in VL testing rates before the COVID-19 pandemic, which persisted during COVID-19.21 In this study, while VL testing decreased between the pre-COVID-19 and COVID-19 periods, this was largely due to continuation of a pre-existing trend of decreased VLs before the COVID-19 pandemic, as demonstrated in the linear regression comparison models. There was also some evidence that level 5 lockdown impacted significantly on VL numbers among 5–14-year-olds who are mostly schoolgoing children, but the impact of lockdown measures was not significant in other groups or at other lockdown levels. Viral load testing can be a proxy marker of both retention in care and the delivery of appropriate monitoring while in care. These findings correlate with other studies that indicated the general preservation of ART clinic visits even during the COVID-19 pandemic.22 We also found VL suppression rates of more than 70% in this study population over both study periods, similar to other sub-Saharan Africa studies pre-COVID-19.24 Viral load suppressions rates in this study were maintained throughout almost two years of the COVID-19 period and a similar period preceding, indicating infants, children and adolescents have maintained adherence to ART regimens. Both these findings suggest that the ART programmes in the district have the robustness to continue to provide similar care to clients already in the programme and on ART despite the pandemic-related disruptions experienced.Several modelling studies and early reviews from LMIC have raised concerns about the sustainability of ART programmes within the fragile healthcare systems in sub-Saharan Africa following the COVID-19 pandemic. Studies that reviewed care among children and adolescents during the COVID-19 pandemic documented decreases in general paediatric admissions and general outpatient and emergency visits across the world, including SA.26 This maintenance of care contrasted sharply with decreases noted over the same time periods with general paediatric hospitalisation rates and outpatient visits. These findings add to the limited data on the impact of the COVID-19 pandemic on paediatric ART programmes that remained robust for those already on treatment. Lessons learned from these programmes can be used to inform other care platforms delivering chronic care to patients.27Previous studies from LMICs have rarely evaluated ART treatment programmes longitudinally over the different COVID-19 waves and various national lockdown levels imposed by a national government. In this study, using excess mortality as a proxy, the linear regressions model indicated that ART programmes were sustained during all varying levels of disruption experienced during varying COVID-19 waves and various lockdown levels. Pre-lockdown stocking up, multi-month prescribing and differentiated ART delivery platforms have been documented as possible reasons for the sustained care seen specifically in the ART programmes.11 In addition, non-governmental support for many of these clinics, including additional staffing, has diminished since 2018, mainly due to funding challenges. The COVID-19 pandemic has exacerbated this.26 Increasing task shifting to clinics, with existing staff shortages, may also be diluting support and specialised care afforded to families deemed at risk of complying with the strict compliance requirements for the SA ART programme. The COVID-19 pandemic has exacerbated the socio-economic strife for many such at-risk families, which may limit their ability further. The trend in VL testing rates away from rather than towards achieving the UNAIDS goal of 95% of children on ART having a suppressed VL requires a more urgent in-depth understanding.Of significance, this study identified a concerning trend of decreasing VL testing, especially in children between four and 15 years of age. The decrease preceded the COVID-19 pandemic and suggests fundamental shifts in ART care may be at play. The VL test guidelines remained the same during the study period, recommending annual VL testing for patients in chronic ART care. In 2019, the South African National Department of Health (NDoH) introduced Dolutegravir to the programme for children and adolescents over 20 kg with a suppressed VL. We would have expected an increase in VL testing in 2019, which was not seen in this study. Apart from guideline changes, service delivery changes may impact the SA ART programme, including the large KZN programme catering to children and adolescents. These include active encouragement of down-referral of children from hospital-centric clinics to primary healthcare clinics and amalgamation of HIV care into general outpatient services in larger facilities. Many of these down-referrals result in a move away from previous child-friendly clinical, social and peer group support, which is much needed.This study focuses on one district in one province of SA and may not reflect specific challenges or strengths in programmes across the country. However, KZN has the largest proportion of patients in HIV care in the country, and the eThekwini district is home to almost 50% of the province. This study did not utilise patient-specific data but rather aggregated facility-level data; therefore, we cannot directly translate the number of VLs performed to the number of patients in care. Of note, this study did not evaluate HIV testing and ART initiation rates which have been found to have decreased with the COVID-19 pandemic in other studies.Despite changes in both lockdown restrictions and the burden of disease, the number of both VL tests done and the percentage of unsuppressed VLs were not markedly impacted by the COVID-19 pandemic. Paediatric VL testing across the eThekwini district, KZN, remained largely robust through the COVID-19 pandemic negating the predicted negative modelled scenarios. However, a long-term trend of slow reduction in the number of VLs done preceding the COVID-19 pandemic requires further evaluation. It may be due to changes in service delivery to children on ART in the district.


Until now this association remains to be discussed.A 49-year-old man presented to the Emergency Department a 7-day after receiving her second dose of BNT162b2 mRNA COVID-19 (Pfizer-BioNTech), and he was diagnosed with pulmonary embolism (PE) with junctional tachycardia on ECG. The biological workup showed an increase in CRP with elevated D-dimer, but no abnormalities in cardiac markers, including troponin and BNP, the COVID-19 testing was negative and absence of thrombocytopenia. The patient was put under curative anticoagulation by rivaroxabon.Studies have reported the association of venous thrombosis after administration of the COVID-19 vaccine with negative FP4 antibodies and normal platelet count which is similar with our patient. Moreover, spike proteins generated by mRNA vaccines can produce a pro-inflammatory state, a cascade of events guiding to endothelial dysfunction and afterwards to the development of venous thrombosis.All the same that some studies association COVID-19 immunizations to the development of VTE, we nevertheless recommend COVID-19 vaccination, due to the rarity of these events, compared to the hypercoagulable effects and other serious complications of COVID-19 infection. •The association between the development of a thromboembolic event following COVID-19 vaccination is very rare.•Studies have reported the association of venous thrombosis after administration of the COVID-19 vaccine with negative FP4 antibodies and normal platelet count which is similar with our patient.•We nevertheless recommend COVID-19 vaccination, due to the rarity of these events, compared to the hypercoagulable effects and other serious complications of COVID-19 infection. COVID-19 vaccines were developed as a result of coordinated global efforts, they were intended for public administration and are now widely available . HoweverWith the frequency number of suspected COVID vaccine-associated thrombosis rises, we report extensive thromboembolism in a 59-year-old man that occurred 7 days after receiving the first dose of the BNT162b2 Pfizer-BioNTech mRNA vaccine.2We report the case of a 49-year-old man, with no medical history, admitted to the emergency department for the management of acute respiratory failure 7 days after receiving the second dose of the Pfizer COVID-19 vaccine 4 days before. On admission, the patient was hemodynamically and neurologically stable, dyspneic with a respiratory rate of 28 cpm/min and a room air SpO2% of 92%, T° = 38.7, weight 95kg with a height of 1.76cm and a BMI of 31.96kg/m2. The examination was unremarkable. ECG found a junctional tachycardia with a HR at 156 bpm , An echoThe history did not indicate any recent bed rest, prolonged travel or surgery in the last 3 months, and given the notion of vaccination and the reports published in this sense, a causal link was made between the vaccination and the pulmonary embolism.The patient was put under curative anticoagulation by rivaroxabon, with a good initial clinical evolution, the junctional tachycardia was regressed spontaneously in sinus rhythm. A report was made to the pharmacovigilance center. and the patient is discharged home and he is followed in consultation with a control 3 months after his release.3In the fight against the COVID-19 pandemic, a collective vaccination campaign is critical. Several vaccines, including Pfizer's (BNT162b2mRNA), Moderna's (mRNA-1273), J&J's (Ad26.COV2.S), and AstraZeneca's (AZD1222), have been approved as a result of these efforts. Nevertheless, adverse effects have been observed following vaccine injections. Rare undesirable damage has been reported such as myocarditis, pericarditis, vascular syndromes, thrombosis complication and other diseases .The association between COVID-19 vaccine and thromboembolic complication is increasingly demonstrated in the literature. The timing of vaccination with the development of thrombosis is nonspecific. Thrombosis can develop within the first 7–10 days .Scientific research are discussing the relevance of vaccine-induced thrombotic thrombocytopenia (VITT) in the thrombosis episodes after COVID-19 vaccination. The VITT condition intently similar to heparin-induced thrombocytopenia (HIT) , becauseSome studies have discussed the resemblance between COVID-19 vaccines and virus COVID-19. COVID-19 infection leads to a major thrombotic state proven by several studies, the same thrombogenic effect can occur after vaccination, the mechanism of which remains unknown until now. Moreover, spike proteins generated by mRNA vaccines can produce a pro-inflammatory state, a cascade of events guiding to endothelial dysfunction and afterwards to the development of venous thrombosis .Indeed, our patient had no risk factor predisposing to the development of acute venous thrombosis, in particular pulmonary embolism, and he tested negative for COVID-19 infection, however the development of this thrombosis due to the mRNA-1273 vaccine is the most reasonable explanation. The formation of emboli may be secondary to a cause other than VITT, with a predilection for the venous circuit after mRNA vaccination. Studies have reported the association of venous thrombosis after administration of the COVID-19 vaccine with negative FP4 antibodies and normal platelet count which is similar with our patient ,16.The SCARE guidelines were used in the writing of this paper .4Despite the fact that some studies association COVID-19 immunizations to the development of VTE, we nevertheless recommend COVID-19 vaccination, due to the rarity of these events, fewer than 0.01% of the overall vaccinated population has been affected. Compared to the hypercoagulable effects and other serious complications of COVID-19 infection are well established by several studies and in the literature. further research is needed to better assess the causality and specificity between vaccine-induced thromboembolism and take into account patient characteristics.Written informed Consent was obtained from the Child's patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.The ethical committee approval was not required give the article type (case report).However, the written consent to publish the clinical data of the patients was given and is available to check by the handling editor if needed.None.CHAYMAE MIRI: Study concept or design, data collection, data analysis or interpretation, writing the paper.AMINE BOUCHLARHEM: Data collection, data analysis.SOUMIA BOULOUIZ: Data collection, data analysis.NOHA EL OUAFI: supervision and data validation.ZAKARIA BAZID: supervision and data validation.This is not an original research project involving human participants in an interventional or an observational study but a case report. This registration is was not required.Chaymae Miri.Written informed Consent was obtained from the patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.Not commissioned, externally peer reviewed.None.


E = 10–19, dependent on the lacquer type) than the oak surfaces treated in the same ways (ΔE = 4–11). There were also confirmed significant impacts of the particular surface treatment on the colour stability as well as significant impacts of wood surface pre-treatment with pigment and stain mordants . In the case of water-based lacquers, the ΔE values ranged between 3 and 11 (according to the coating system type). The results show that an appropriate UV absorbent combined with an appropriate lignin stabilizer and pigment mordant may enable attaining the required colour stability for a given surface treatment applied on a given wood species.This work evaluates the effects of accelerated aging on the discolouration of surface-treated spruce wood and oak wood coated with solvent-based polyurethane lacquers, and surface-treated spruce wood coated with water-based transparent coating systems. All concerned coating materials were intended for indoor use. It was also explored how the colour stability of spruce wood and oak wood surfaces treated with solvent-based polyurethane lacquers was affected by wood surface layer modifications with pigment or stain mordants applied before these lacquers. Another issue studied was how the lignin stabilizer admixed into the primer and pigments admixed into the top coating layers affected the stability of water-based coating systems on spruce. The experimental results showed that the accelerated aging process with a simulation of indoor conditions induced significant discolouration of wood surfaces coated with solvent-based polyurethane lacquers and water-based coating systems. There were also confirmed significant impacts of all the studied factors . The spruce wood surfaces coated with solvent-based polyurethane lacquers were less stable (Δ Surfaces of almost all materials exposed to outdoor conditions are affected by various types of radiation, moisture, heat, and pollutants. Acting in many interactions, these factors cause the surfaces to degrade progressively ,2. This Moreover, the external environment negatively affects the ST quality as such ,26,27,28The problem is complex, demanding much effort and a multitask approach. Research is also needed in the context of today’s demands on ST durability and preserving the original quality. This is why the research has been oriented to improve ST colour stability, as well as overall stability, by means of targeted modification of the substrate and the coating material ,34,35,36Distinctly, not as much interest has been given to the ageing process of sur-face-treated wood purposed for indoor conditions. The works ,38,39 shThe aim of this work was to evaluate the effects of the accelerated ageing process on the discolouration of surface-treated spruce wood and oak wood coated with solvent-based polyurethane lacquers, and of spruce wood coated with water-based coating systems intended for indoor use. Another objective was to analyse the impacts of modification of wood surface layers with pigment or stain mordants applied before the solvent-based polyurethane lacquers and to analyse in which way lignin stabiliser admixed to the primer and pigments admixed to the top layer may impact the colour stability of spruce wood coated with water-based lacquers.Meeting the aims of the work required to lay out two experiments. The colour stability of four types of polyurethane lacquers was tested in the first experiment, labelled as PUR-1, PUR-2, PUR-3, and PUR-4 . The lacquers were two-component, solvent-based, transparent polyurethane lacquers intended for the surface finishing of furniture intended for indoor exposure, with improved mechanical and chemical resistance. The two last lacquers were identical, except that the lacquer PUR-4 was supplemented with a UV radiation adsorber acting on the benzotriazole base. In one case, the lacquers were applied directly on spruce and oak wood specimens sized 100 mm × 50 mm × 10 mm (length × width × thickness). In another case, the spruce wood surfaces were treated with a pigment mordant and oak wood specimens with a stain mordant, with the aim of inspecting mordant effects on the colour stability. The specimens stained in this way were finished with the tested lacquers. For each surface treatment type and for each wood species, there were prepared by 5 specimens, representing 80 in total. In the second experiment, four three-layer coating systems (CS) were tested for the surface treatment of wooden frames on the interior side of wood–aluminium windows. All the used coating systems were water-based. There was a mixture of acryl/alkyd or polyurethane resins and their combinations. All the coating materials were transparent. In this experiment, also studied was the influence of lignin stabiliser added to the primer, with the aim to slow down the colour degradation process. Another study aspect was to inspect in what way soft pigmentation would influence surface layer degradation. The pigments were admixed in amounts not suppressing the original spruce wood texture. The arrangement of CSs is in The specimens with surfaces treated in this way were exposed to accelerated aging in a xenotest Q-SUN Xe-3-HS . The regimen simulated outdoor conditions when the material was exposed to radiation but protected from rain . The ind−2 at a wavelength of λ = 340 nm. These values correspond to the average radiation intensity for the temperate zone. The temperature checked on a black panel reflects the maximum temperature value on the surface. The set air temperature accelerates the modification of surface properties. In the case of polyurethane lacquers, the colour changes were inspected after 50, 100, 200, 300, 400, and 500 h. On each specimen, the colour was measured at ten spots, so the total number of measurements for each surface ST mode was 50. In the case of water-based coating systems, the aging period was 700 h. In accordance with the standard , the radL*, a*, and b* were measured on all specimens before and during the aging process. The measuring equipment was a spectrophotometer Spectro-Guide 45/0 gloss . The discolouration extent was expressed through the total colour difference ΔE, calculated according to the following equation.The colour space coordinates Note tgat5 the indices “2The results were processed in the programme STATISTICA version 10.0. The basic statistical characteristics  were determined with using the descriptive statistics. The impacts of the studied factors on the given properties were evaluated with multi-way variance analysis (MANOVA) and Duncan’s test.L*, a*, b*, and additional statistical characteristics measured during the aging process of spruce wood coated with polyurethane lacquers of four types are summarized in The average values of colour coordinates L*, a*, and b* of spruce wood treated with polyurethane lacquers exhibited differences before aging. These differences were not much pronounced; nevertheless, they reflected the fact that the tested transparent lacquers were not absolutely pure. This was especially evident for the lacquers PUR-1 and PUR-2. In these cases, the coordinate b* value was shifted toward more saturated yellow, and the a* value was shifted toward red, in comparison to the native wood surface. In the presence of a slight lightness reduction, the spruce wood exhibited a darker yellow-brown hue after surface finishing. The values of the total colour difference ΔE were within a range between 1 and 2.0, which corresponds to the second degree of the six-degree scale [ee scale . These dThe lightness of surface-treated spruce wood decreased with advancing aging time in all cases . After 5The values of coordinate a* increased with aging time up to the end of the aging process. This means that the coordinate a* was growing moderately towards red saturation. A qualitatively similar course was also recorded for the coordinate b*, with the values step-by-step shifting to yellow. As a result, the surfaces treated with the tested polyurethane lacquers darkened progressively, turning to a darker yellow-brown hue compared to the referential specimens .E  significantly improved the colour stability of the surface treatment. After 200 aging hours, the overall colour differences in the spruce wood surface finished with PUR-4 corresponded to degree 4 . After the aging process had finished, the discolouration corresponded to degree 5. The protective substance applied in this coating system significantly decelerated photodegradation. Nevertheless, it was not effective enough to suppress the colour changes on the spruce wood surface to negligible changes.The data concerning the colour variation on the surface-treated spruce wood preliminary modified with pigment stain mordents are presented in The pre-treatment of the spruce wood surface with a pigment stain mordant commonly used for attaining the required colour hue of the wood surface also enabled guaranteeing of better colour homogeneity. In this case, the changes in the colour coordinates differed from the corresponding changes obtained for non-stained surfaces, both in quality and quantity . In almoThe same lacquers were also applied onto oak wood. The results are summarized in The results showed that the colour stability of surface-treated oak wood was different from spruce in extent and patterns . In geneE reach beyond 12. The discolouration of the surfaces finished with PUR-2 and PUR-4 was between degrees 3 and 4, in the case of PUR-1 and PUR-3, it was degree 5 of the six-degree scale. Better colour stability is supposedly due to the different chemical structures of oak wood, especially extractives causing the oak wood to be darker than spruce. The works [In no case did the total colour difference value Δhe works ,23,33,37a* values moderately decreased (except PUR-4), while the coordinate b* values increased. In this case, the highest colour stability was observed for the surfaces treated with PUR-1, followed by PUR-4 coated surfaces, and finishing with PUR-2. The results indicate more conspicuous discolouration in the stained oak wood compared to unstained  was 82. After admixing the white pigment , the average lightness value rose to 86. With advancing irradiation time, in all cases, these lightness values moderately decreased until the aging process was finished.The basic statistical characteristics of the colour coordinates corresponding to the particular accelerated ageing phases are in a* values in the particular surface treatment types ranged between 2 and 4. With progressing aging, the coordinate a* values increased in all cases, which means that this coordinate shifted towards a more saturated red colour .a*, b* moderately increased with aging time. As a result, the surfaces coated with the tested polyurethane lacquers became darker, shifting to darker yellow-brownish hues compared to the referential specimens. In general, we may declare that, after finishing the aging process, the discolouration of the surface-treated oak wood was less distinct compared to the spruce wood. The lightness of surface-treated spruce wood and oak wood coated with polyurethane lacquers decreased with aging. The values of coordinates From the viewpoint of colour stability, the ranking of spruce wood surfaces coated with the discussed lacquers was different from oak. In both cases, the best colour stability was found for the lacquer PUR-4 supplemented with UV absorbent. The poorest colour stability in the surface-treated spruce wood was observed for the lacquer PUR-3, and for the oak wood, it was the lacquer PUR-1.The variation in colour coordinates in surface-treated spruce wood and oak wood coated with identical lacquers showed qualitative and quantitative differences between the surfaces pre-treated with pigment or stain mordants and the surfaces without this pre-treatment. From this viewpoint, there were also observed differences in the ranking according to the surface colour stability.Pre-treatment of spruce wood surfaces with pigment/stain mordants improved the overall colour stability. Nevertheless, the accelerated aging-induced discolouration remained significant. In the case of oak wood, no positive influence of mordant treatment on colour stability was detected. E. The most conspicuous change was observed in the spruce wood coated with the system CS-1, with all three layers transparent and colourless, without any modification. Lignin stabilizer admixed to the primer and white pigment admixed to the top layer significantly improved the colour stability of the surface-treated spruce wood (CS-4).Similarly, spruce wood surfaces coated with water-based coating systems exhibited distinct discolouration associated with the accelerated aging process. There were noticeable differences between the studied coating systems in all three colour coordinates and in the resulting total colour difference ΔThe analysis of the results allows drawing of the conclusion that the colour variations in the studied surface-treated wood species subject to the accelerated aging process are mainly caused by colour degradation of the surface wood layers on their own.