Detecting colorectal cancer using genetic and epigenetic biomarkers: screening and diagnosis.

Colorectal cancer (CRC) is one of the most frequent types of cancer, with high incidence rates and mortality globally. The extended timeframe for developing CRC allows for the potential screening and early identification of the disease. Furthermore, studies have shown that survival rates for patients with cancer are increased when diagnoses are made at earlier stages. Recent research suggests that the development of CRC, including its precancerous lesion, is influenced not only by genetic factors but also by epigenetic variables. Studies suggest epigenetics plays a significant role in cancer development, particularly CRC. While this approach is still in its early stages and faces challenges due to the variability of CRC, it shows promise as a potential method for understanding and addressing the disease. This review examined the current evidence supporting genetic and epigenetic biomarkers for screening and diagnosis. In addition, we also discussed the feasibility of translating these methodologies into clinical settings. Several markers show promising potential, including the methylation of vimentin (VIM), syndecan-2 (SDC2), and septin 9 (SEPT9). However, their application as screening and diagnostic tools, particularly for early-stage CRC, has not been fully optimized, and their effectiveness needs validation in large, multi-center patient populations. Extensive trials and further investigation are required to translate genetic and epigenetic biomarkers into practical clinical use. biomarkers, diagnostic biomarkers.

A systematic review and meta-analysis of HIV transmission risk behaviors, genetic variations, and antiretroviral (ARV) resistance in LGBT populations.

Background: Currently, human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) has become one of the major health problems worldwide, including Indonesia. East Java is one of the provinces in Indonesia with the highest prevalence of HIV infection. One of the causes of HIV infection transmission is lesbian, gay, bisexual, and transgender (LGBT) practice. Furthermore, the treatment using antiretroviral (ARV) drugs in HIV-1 patients can fail due to the presence of HIV drug resistance. Objective: The aim of this study is to identify the behavior at risk of HIV transmission among LGBT, patterns of genetic variation and antiretroviral (ARV) resistance. Methods: A systematic review and meta-analysis based on the PRISMA guidelines was conducted. We searched three databases including PubMed, ScienceDirect, and Google scholar for studies investigating the non-heterosexual behavior as risk factor of HIV infection and antiretroviral resistance. Only studies published in English are considered. The adjusted estimates of the risk were carried out using best-adjusted OR with 95% confidence interval (CI) and significant p value < 0.05. Results: In the quantitative analysis of HIV infection risk factors, a total of 13 studies were included, which investigated non-heterosexual behavior as a potential factor. The studies involved a total of 37,129 participants, comprising 10,449 individuals in the non-heterosexual behavior group (LGBTQ+) and 26,680 individuals in the heterosexual group. The majority of the participants in this study were from the USA, Japan, China, and Brazil, and the main HIV subgenotypes were B and CRF. Additionally, the antiretroviral resistance of HIV patients was examined, involving a total of 3062 individuals, with 1296 individuals in the non-heterosexual behavior group and 1766 individuals in the heterosexual group. Our calculation showed that non-heterosexual behavior was significant as risk factor of HIV infection (OR = 2.17, 95% CI = 1.94-2.43, p < 0.001) and antiretroviral resistance (OR = 1.31, 95% CI = 1.00-1.71, p = 0.05). Conclusion: This study concludes that non heterosexual behavior is significant risk factor of HIV infection. A quite prevalent of antiretroviral resistance were found among non heterosexual behavior. The main subgenotype of HIV are B and CRF.

Impact TB co-infections on immune tolerance among people living with HIV: a systematic review.

BACKGROUND: The high-burden regions of Sub-Saharan Africa, which accounted for greater than 70% of the HIV epidemic, are disproportionately affected by the high rates of TB coinfection. This might be explained by, the low immune tolerance of the population due to malnutrition and chronic infections aggravating immune suppression. In this review, we discuss the immunopathogenesis of this common co-infection that causes significant morbidity and mortality in people living with HIV globally. METHODS: We used published studies using a two-step search strategy. Initial search of Pub Med Central and Google Scholar was undertaken followed by an analysis of the keywords. A second search using all the reference list of all identified reports and articles was searched for additional studies. Literature published as of January 1, 1981, that meets the inclusion criteria were considered. Qualitative data was extracted from papers included in the review. RESULT: Mortality occurs at both ends of the immunological spectrum of TB at one end HIV uninfected patient dies from asphyxiation from acute massive hemoptysis due to cavitary TB; at the other end, and far more frequently HIV-infected patient with disseminated TB dies from overwhelming infection with less evidence of focal pathology. There is no clear sign that the HIV-TB epidemic is slowing, especially considering the emergence of increasingly drug-resistant strains of MTB. A major challenge for the future is to discover immune correlates of TB protection and TB disease risk. Failure to define this conclusively has hindered TB prevention strategies, including the design of new TB vaccines to replace BCG, which provides only shortlived efficacy, prevents severe forms of the extra-pulmonary disease and is contraindicated in PLHIV. CONCLUSION: Understanding TB and HIV infection through immunological advances needs to be combined to describe the complex interactions between TB and HIV and the effects of ART. The complex interactions between the individual components of innate and acquired immune responses to TB and HIV infection is also likely to be the next step forward.

Seroprevalence of SARS-CoV-2 anti-spike IgG antibody among COVID-19 vaccinated individuals residing in Surabaya, East Java, Indonesia.

Background: To limit the SARS-CoV-2 transmission, the Indonesian government launched a COVID-19 vaccination program in January 2021. Studies on the clinical treatment and implementation of COVID-19 vaccination have shown promising results; however, it is necessary to estimate the effectiveness of the vaccines. With the ongoing COVID-19 pandemic, studies have highlighted the impact of COVID-19 vaccines, especially CoronaVac, on Indonesian healthcare workers. To get a better picture of how the vaccines work in Indonesia, it is necessary to estimate the prevalence of SARS-CoV-2 anti-S IgG antibody induced by the COVID-19 vaccine in individuals who have already received two-to-three doses of vaccines. Materials and Methods: Four-hundred and ninety-six whole-blood samples were collected from participants residing in Surabaya, East Java, Indonesia, who received a minimum of a two-dose COVID-19 vaccine. Serums were then isolated from the blood and subjected to detect SARS-CoV-2 anti-S IgG antibodies using a lateral flow immunochromatographic assay. Results: The prevalence of positive anti-S-IgG antibodies was 91.7% (455/496) in all participants receiving a minimum of a two-dose COVID-19 vaccine. As many as 209 (85.3%) and 141 (96.6%) participants were seropositive for receiving CoronaVac and AstraZeneca, respectively. Meanwhile, all participants receiving two-dose CoronaVac with one booster dose of Moderna (105/100%) were seropositive (p < 0.05). Age, comorbidity, and time after the last vaccine were significantly correlated with seropositivity (p < 0.05). Conclusion: Different vaccines might produce different antibody responses. Adopting a stronger policy regarding the administration of booster doses might be beneficial to elicit positive anti-S-IgG antibodies, especially among older individuals, those with comorbid diseases, and those with a longer time after the second vaccination dose.

SARS-CoV-2 lineages circulating during the first wave of the pandemic in North Sumatra, Indonesia.

Objectives: To determine the lineage distribution of the virus during the first wave of the pandemic in North Sumatra, Indonesia. Methods: A total of 20 samples with positive results based on reverse transcription-polymerase chain reaction were selected for virus culture and then performed whole-genome sequence analysis using next-generation sequencing which was applied by the Illumina MiSeq instrument. Results: Whole-genome sequence analysis revealed that the majority of our samples belong to lineages B.1.468 (n = 10), B.1 (n = 5), B.1.1 (n = 2), B.1.1.398 (n = 2), and B.6 (n = 1). Other unique amino acid mutations found in our samples were present in A58T on non-structural protein (NSP3) (70%), P323L on NSP12 (95%), Q57H on NS3 protein (75%), and D614G on S (100%). Conclusion: The SARS-CoV-2 lineage B.1.468 may be the main virus variant circulating in North Sumatra at the beginning of the emergence of COVID-19 cases in this province.

A household survey of intrafamily norovirus transmission.

Norovirus (NoV) is a leading cause of epidemic and sporadic gastroenteritis in people of all ages. Humans are the primary source of NoV and household contact is one of the risk factors for NoV transmission. However, the mechanisms underlying person-to-person NoV transmission are poorly understood. Here we conducted a survey to profile the frequency and characteristics of intrafamily NoV transmission. Stool samples were collected every week from three households between 2016 and 2020; the total number of samples was 1105. The detection of NoV and the genotyping were performed by reverse transcription-polymerase chain reaction targeting the capsid region and direct sequencing methods. NoV was detected in 3.4% of all samples. Eight NoV genotypes were identified. The most common genotype was GII.17, followed in order by GII.6, GI.6, GII.4, GI.3, and GI.2/GI.8/GI.9. Most NoV-positive samples were obtained from asymptomatic individuals. The highest number of NoV transmissions was found in household 3 (6 infections), followed by household 2 (2 infections), while household 1 had no NoV transmission, suggesting that asymptomatic NoV carriers play a major role in infection as NoV reservoirs in the households. Further clarification of the mode of infection will contribute to improved understanding and an appropriate prevention.

HAART induced inflammation, toxicity and its determinants among HIV positive children in Addis Ababa, Ethiopia.

Background: Highly Active Antiretroviral therapy (HAART) plays significant role in reduction of mortality among children infected with HIV. Despite the inevitable impact of HAART on inflammation and toxicity, there is limited evidence on its impact among children in Ethiopia. Moreover, evidence on contributing factors to toxicity has been poorly described. Hence, we evaluated HAART induced inflammation and toxicity among children taking HAART in Ethiopia. Method: This cross-sectional study was conducted among children (<15 years old) taking HAART in Ethiopia. Stored plasma samples and secondary data from a previous study on HIV-1 treatment failure were used for this analysis. By 2018, a total of 554 children were recruited from randomly selected 43 health facilities in Ethiopia. The different levels of liver (SGPT), renal (Creatinine) and hematologic toxicity (Hemoglobin) toxicity were assessed using established cut-off value. Inflammatory biomarkers (CRP and vitamin-D) were also determined. Laboratory tests were done at the national clinical chemistry laboratory. Clinical and baseline laboratory data were retrieved from the participant's medical record. Questionnaire was also administered to study guardians to assess individual factors to inflammation and toxicity. Descriptive statistics was used to summarize the characteristics of the study participants. Multivariable analysis was conducted and considered significant at P < 0.05. Result: Overall 363 (65.6%) and 199 (36%) of children taking HAART in Ethiopia developed some level of inflammation and vitamin-D in-sufficiency, respectively. A quarter of the children 140 (25.3%) were at Grade-4 liver toxicity while renal toxicity were 16 (2.9%). A third 275 (29.6%) of the children also developed anemia. Children who were on TDF+3 TC + EFV, those who were not virally suppressed and children with liver toxicity were at 17.84 (95%CI = 16.98, 18.82), 2.2 (95%CI = 1.67, 2.88) and 1.20 (95%CI = 1.14, 1.93) times risk of inflammation, respectively. Children on TDF+3 TC + EFV, those with CD4 count of <200 cells/mm3 and with renal toxicity were at 4.10 (95%CI = 1.64, 6.89), 2.16(95%CI = 1.31, 4.26) and 5.94 (95%CI = 1.18, 29.89) times risk of vitamin-D in-sufficiency, respectively. Predictors of liver toxicity were history of HAART substitution (AOR = 4.66; 95%CI = 1.84, 6.04) and being bedridden (AOR = 3.56; 95%CI = 2.01, 4.71). Children from HIV positive mother were at 4.07 (95%CI = 2.30, 6.09) times risk of renal toxicity while the different type of HAARTs had different level of risk for renal toxicity AZT+3 TC + EFV (AOR = 17.63; 95%CI = 18.25, 27.54); AZT+3 TC + NVP (AOR = 22.48; 95%CI = 13.93, 29.31); d4t+3 TC + EFV (AOR = 4.34; 95%CI = 2.51, 6.80) and d4t+3 TC + NVP (AOR = 18.91; 95%CI = 4.87, 27.74) compared to those who were on TDF+3 TC + NVP. Similarly, children who were on AZT+3 TC + EFV were at 4.92 (95%CI = 1.86, 12.70) times risk of anemia compared to those who were on TDF+ 3 TC + EFZ. Conclusion: The high level of HAART induced inflammation and liver toxicity among children calls for the program to consider safer regimens for pediatric patients. Moreover, the high proportion of vitamin-D in-sufficiency requires program level supplement. The impact of TDF+3 TC + EFV on inflammation and vitamin-D deficiency calls for the program to revise this regimen.

The evaluation results of proposed antigen rapid diagnostic tests for COVID-19: some possible factors might influence.

PURPOSE: In addition to existing gold standard qRT-PCR methods, there is a need to develop reliable rapid tests for infection control with early notification of COVID-19 cases to enable effective outbreak management. We evaluated the validity of the three Ag-RDT kits proposed by some companies in different countries by using qRT-PCR and analyzed its results. METHODS: Each of the three Ag-RDT kits (namely A, B, and C) was tested with 90 samples, consisting of samples with Ct ≤ 25, samples with Ct > 25, and negative SARS-CoV-2 PCR samples. RESULTS: This study showed that for samples with Ct > 25, all the three kits could not detect SARS-CoV-2 Ag (0% sensitivity) but showed 100% specificity. Meanwhile, for samples with Ct ≤ 25, kit C was the best (76.7% sensitivity and 100% specificity). The PPV of the three kits was 100%, but their NPV ranged 63-84.8%. Kit C showed the best accuracy (89.9%). Some factors might influence the results of evaluation, such as variation of virus proteins and transportation-storage of the kits. CONCLUSION: The overall specificity of the three kits for all samples was high; however, all of them have not met the minimum performance requirements of ≥ 80% sensitivity for samples with Ct ≤ 25. The validation test is much necessary to be carried out by the authority in national health care to ensure the feasibility of the kit for point-of-care testing (POCT) of COVID-19. Some factors that might influence should be anticipated to increase their sensitivities and specificities.

Complete genome analyses of G12P[8] rotavirus strains from hospitalized children in Surabaya, Indonesia, 2017-2018.

Rotavirus A (RVA) is a major viral cause of acute gastroenteritis (AGE) worldwide. G12 RVA strains have emerged globally since 2007. There has been no report of the whole genome sequences of G12 RVAs in Indonesia. We performed the complete genome analysis by the next-generation sequencing of five G12 strains from hospitalized children with AGE in Surabaya from 2017 to 2018. All five G12 strains were Wa-like strains (G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1) and were clustered into lineage-III of VP7 gene phylogenetic tree. STM430 sample was observed as a mixed-infection between G12 and G1 strains: G12/G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. A phylogenetic tree analysis revealed that all five Indonesian G12 strains (SOEP379, STM371, STM413, STM430, and STM433) were genetically close to each other in all 11 genome segments with 98.0%-100% nucleotide identities, except VP3 and NSP4 of STM430, suggesting that these strains have originated from a similar ancestral G12 RVA. The VP3 and NSP4 genome segments of STM430-G12P[8] were separated phylogenetically from those of the other four G12 strains, probably due to intra-genotype reassortment between the G12 and G1 Wa-like strains. The change from G12P[6] lineage-II in 2007 to G12P[8] lineage-III 2017-2018 suggests the evolution and diversity of G12 RVAs in Indonesia over the past approximately 10 years.

SARS-CoV-2 IgG antibody status in unvaccinated and 2-dose vaccinated Indonesians by AstraZeneca.

Indonesia began deploying a COVID-19 vaccine in January 2021, prioritising vaccination for high-risk groups such as healthcare workers, the elderly and those with comorbidities, and ending with the general public due to limited vaccine availability. Our study aimed to evaluate antibody response in Indonesians who had received two doses of the vaccine vs. those who had not. The study design was a cohort study involving 46 unvaccinated people and 23 people who had received the second dose of the AstraZeneca vaccine in three months. Methods used for the qualitative and quantitative detection of IgG antibodies included rapid RI-GHA and ELISA tests. Findings showed that positive IgG antibodies qualitatively detected by the rapid RI-GHA test were significantly higher in those vaccinated (60.9%) than in unvaccinated people (26.1%). Using the ELISA assay, all vaccinated individuals qualitatively showed positive antibodies (cut-off ≥4.33 BAU/ml), and the average quantitative titer of anti-SARS-CoV-2 s-RBD IgG was significantly higher in vaccinated (157.06±238.68 BAU/ml) than in unvaccinated (51.90±87.60 BAU/ml) individuals. Some unvaccinated individuals with no history of infection were found to have anti-SARS-CoV-2 antibodies that may have been previously asymptomatic, although their mean antibody titers were certainly lower than those in the 2-dose group. Approximately 56% of vaccinated individuals had antibody titers above 60 BAU/ml as a cut-off for protective threshold, a significantly higher proportion than unvaccinated individuals. In conclusion, vaccination with two doses AstraZeneca increased anti-SARS-CoV-2 antibodies which resulted in enhanced immunity against symptomatic COVID-19.

Fluorescence spectrophotometry for COVID-19 determination in clinical swab samples.

Considering the limitations of the assays currently available for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its emerging variants, a simple and rapid method using fluorescence spectrophotometry was developed to detect coronavirus disease 2019 (COVID-19). Forty clinical swab samples were collected from the nasopharyngeal and oropharyngeal cavities of COVID-19-positive and -negative. Each sample was divided into two parts. The first part of the samples was analyzed using reverse transcription-polymerase chain reaction (RT-qPCR) as the control method to identify COVID-19-positive and -negative samples. The second part of the samples was analyzed using fluorescence spectrophotometry. Fluorescence measurements were performed at excitation and emission wavelengths ranging from 200 to 800 nm. Twenty COVID-19-positive samples and twenty COVID-19-negative samples were detected based on RT-qPCR results. The fluorescence spectrum data indicated that the COVID-19-positive and -negative samples had significantly different characteristics. All positive samples could be distinguished from negative samples by fluorescence spectrophotometry. Principal component analysis showed that COVID-19-positive samples were clustered separately from COVID-19-negative samples. The specificity and accuracy of this experiment reached 100%. Limit of detection (LOD) obtained 42.20 copies/ml (Ct value of 33.65 cycles) for E gene and 63.60 copies/ml (Ct value of 31.36 cycles) for ORF1ab gene. This identification process only required 4 min. Thus, this technique offers an efficient and accurate method to identify an individual with active SARS-CoV-2 infection and can be easily adapted for the early investigation of COVID-19, in general.

Synthesis and assessment of copper-based nanoparticles as a surface coating agent for antiviral properties against SARS-CoV-2.

To halt the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), governments around the world have imposed policies, such as lockdowns, mandatory mask wearing, and social distancing. The application of disinfecting materials in shared public facilities can be an additional measure to control the spread of the virus. Copper is a prominent material with antibacterial and antiviral effects. In this study, we synthesized copper nanoparticles (CuNPs) as a surface coating agent and assessed their antiviral activity against SARS-CoV-2. CuNPs with a mean size of 254 nm in diameter were synthesized from copper sulfate as a source and were predominantly composed of copper oxide. The synthesized CuNPs were mixed with resin-based paint (CuNP/paint) and sprayed on the surface of stainless steel remnants. SARS-CoV-2 lost 97.8% infectivity on the CuNP/paint-coated surface after 30 min of exposure and more than 99.995% infectivity after 1 h of exposure. The inactivation rate was approximately 36-fold faster than that on the paint alone-coated and uncoated surfaces. The CuNP/paint-coated surface showed powerful inactivation of SARS-CoV-2 infectivity, although further study is needed to elucidate the inactivation mechanisms. Applications of CuNP/paint coatings to public or hospital facilities and other commonly touched areas are expected to be beneficial.

Viral shedding and the durability of immunoglobulin G antibodies to severe acute respiratory syndrome coronavirus 2.

We followed 45 participants in Surabaya, Indonesia, for 10 months and compared their PCR and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) results. As much as 13 out of 45 participants were IgG seropositive at least once while the remaining 32 stayed IgG seronegative throughout the study. Among 13 seropositive participants, 9 were consecutively seropositive at least twice and were eligible for IgG longevity evaluation. The duration of IgG detection varied from 47 to ≥233 days. We observed intermittent re-positive PCR results suggestive of viral shedding in participants with a longer duration of IgG detection.

Identification and Isolation of Japanese Encephalitis Virus Genotype IV from Culex vishnui Collected in Bali, Indonesia in 2019.

Japanese encephalitis virus (JEV) is transmitted between swine, migratory birds, and Culex mosquitoes, and has circulated indigenously in Asia for almost a century. Despite being the country with the highest JEV diversity, surveillance targeting of Indonesia's vectors is scarce. This study collected mosquitoes from several locations in Tabanan Regency, Bali Island, Indonesia. We captured and classified 3,032 adult Culex mosquitoes into seven species, with Culex vishnui subgroup mosquitoes making up approximately 90% of the total. Japanese encephalitis virus was identified by next-generation sequencing (NGS) analysis of a Cx. vishnui mosquito pool. Genetic and phylogenetic analysis revealed the JEV as genotype (G) IV. The nucleotide identity was 99% with other JEV GIV isolates obtained from swine sera in 2017 on Bali Island and from a human patient in Australia with a travel history to Bali in 2019. This finding indicated that JEV GIV persists in restricted areas and is circulating between swine-mosquito vectors.

Potential Misdiagnosis between COVID-19 and Dengue Infection Using Rapid Serological Test.

The coronavirus disease 2019 (COVID-19) pandemic that has a significant rapid transmission is an international public health concern. Several dengue-endemic countries reported similar clinical and laboratory features between COVID-19 and dengue in the early incubation period, and thus discerning the infection is difficult. As a dengue-endemic country, Indonesia also poses the same challenge during the COVID-19 outbreak. This current study analyzed the IgG and IgM profiles from COVID-19 patients by using a serological SARS-CoV-2 and dengue rapid test. In addition, 38 sera from healthy individuals (pre-COVID-19 date) were analyzed using a dengue rapid test. Among 120 samples, 4 samples indicated dengue IgG positive. However, IgM, NS1, and RT-PCR analyses showed negative results. Interestingly, regarding seropositivity of NS1 and DENV IgG from healthy individuals (pre COVID-19 infection), two samples were positive DENV IgG, while one of them was positive NS1. This suggested that in the dengue-endemic area, many people have already experienced dengue and have immunity against dengue virus. There is also the possibility of antibody cross-reactivity between COVID-19 and dengue infection. This also emphasizes the high demand for a rapid method with high sensitivity and specificity that can distinguish between SARS-CoV-2 and dengue.

Prevalence and Distribution of Rotavirus Genotypes Among Children With Acute Gastroenteritis in Areas Other Than Java Island, Indonesia, 2016-2018.

Group A rotaviruses (RVAs) are the leading cause of acute gastroenteritis, which is often associated with severe symptoms in children under 5 years old. Genetic reassortments and interspecies transmission commonly occur, resulting in a great diversity of RVA circulating in the world. The aim of this study is to determine the prevalence and distribution of RVA genotypes among children in Indonesia over the years 2016-2018 across representative areas of the country. Stool samples were collected from 202 pediatric patients with acute gastroenteritis in three regions of Indonesia (West Nusa Tenggara, South Sumatra, and West Papua) in 2016-2018. Rotavirus G and P genotypes were determined by reverse transcription PCR (RT-PCR) and direct sequencing analysis. The prevalences of RVA in South Sumatra (55.4%) and West Papua (54.0%) were significantly higher than that in East Java (31.7%) as determined in our previous study. The prevalence in West Nusa Tenggara (42.6%) was the lowest among three regions, but higher than that in East Java. Interestingly, equine-like G3 rotavirus strains were found as predominant strains in South Sumatra in 2016 and in West Papua in 2017-2018. Moreover, the equine-like G3 strains in South Sumatra detected in 2016 were completely replaced by human G1 and G2 in 2018. In conclusion, RVA infection in South Sumatra and West Papua was highly endemic. Equine-like G3 strains were also spread to South Sumatra (West Indonesia) and West Papua (East Indonesia), as well as Java Island. Dynamic change in rotavirus genotypes from equine-like G3 to human genotypes was also observed. Continuous monitoring may be warranted in isolated areas in Indonesia.

Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global health problem that causes millions of deaths worldwide. The clinical manifestation of COVID-19 widely varies from asymptomatic infection to severe pneumonia and systemic inflammatory disease. It is thought that host genetic variability may affect the host's response to the virus infection and thus cause severity of the disease. The SARS-CoV-2 virus requires interaction with its receptor complex in the host cells before infection. The transmembrane protease serine 2 (TMPRSS2) has been identified as one of the key molecules involved in SARS-CoV-2 virus receptor binding and cell invasion. Therefore, in this study, we investigated the correlation between a genetic variant within the human TMPRSS2 gene and COVID-19 severity and viral load. RESULTS: We genotyped 95 patients with COVID-19 hospitalised in Dr Soetomo General Hospital and Indrapura Field Hospital (Surabaya, Indonesia) for the TMPRSS2 p.Val160Met polymorphism. Polymorphism was detected using a TaqMan assay. We then analysed the association between the presence of the genetic variant and disease severity and viral load. We did not observe any correlation between the presence of TMPRSS2 genetic variant and the severity of the disease. However, we identified a significant association between the p.Val160Met polymorphism and the SARS-CoV-2 viral load, as estimated by the Ct value of the diagnostic nucleic acid amplification test. Furthermore, we observed a trend of association between the presence of the C allele and the mortality rate in patients with severe COVID-19. CONCLUSION: Our data indicate a possible association between TMPRSS2 p.Val160Met polymorphism and SARS-CoV-2 infectivity and the outcome of COVID-19.

Seroepidemiological study of SARS-CoV-2 infection in East Java, Indonesia.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic, including Indonesia. However, there are only limited data regarding the precise prevalence of the COVID-19 pandemic in Indonesia. Here, to estimate the magnitude of SARS-CoV-2 infection in East Java, Indonesia, we investigated the prevalence of immunoglobulin G (IgG) antibodies. We enrolled 1,819 individuals from June to December 2020 and observed that the subjects' overall prevalence of IgG antibody to SARS-CoV-2 was 11.4% (207/1,819). The prevalence of anti-SARS-CoV-2 antibodies differed significantly between the job/occupation groups (P = 0.0001). A greater prevalence of IgG was detected in laboratory technicians (who take samples from suspected cases and deal with polymerase chain reaction [PCR] procedures, 22.2%) compared to medical personnel who see and take direct care of patients with COVID-19 (e.g., physicians and nurses, 6.0%), other staff in medical facilities (2.9%), general population (12.1%) and non-COVID-19 patients (14.6%). The highest prevalence among age groups was in the 40-49-year-olds (14.8%), and the lowest prevalence was in the 20-29-year-olds (7.4%). However, the younger population still showed a higher prevalence than generally reported, suggesting greater exposure to the virus but less susceptibility to the disease. A geographical difference was also observed: a higher prevalence in Surabaya (13.1%) than in Jombang (9.9%). In conclusion, the COVID-19 outbreak among asymptomatic populations was characterized by a high prevalence of infection in East Java, Indonesia.

Systematic review of gut microbiota and attention-deficit hyperactivity disorder (ADHD).

BACKGROUND: Gut-brain axis (GBA) is a system widely studied nowadays, especially in the neuropsychiatry field. It is postulated to correlate with many psychiatric conditions, one of them being attention-deficit hyperactivity disorder (ADHD). ADHD is a disorder that affects many aspects of life, including but not limited to financial, psychosocial, and cultural aspects. Multiple studies have made a comparison of the gut microbiota between ADHD and healthy controls. Our aims were to review the existing studies analyzing the gut microbiota between human samples in ADHD and healthy individuals. METHODS: The literature was obtained using Google Scholar, Pubmed, and Science Direct search engine. The keywords used were "ADHD", "gut microbiota", "stool", "gut", and "microbiota". The selected studies were all case-control studies, which identify the gut microbiota between ADHD and healthy individuals. RESULT: We found six studies which were eligible for review. The model and methods of each study is different. Forty-nine bacterial taxa were found, yet none of them can explain the precise relationship between ADHD and the gut microbiota. Bifidobacterium was found in higher amount in ADHD patients, but other study stated that the abundance of this genus was lower in ADHD with post-micronutrient treatment. This may suggest that micronutrient can modulate the population of Bifidobacterium and improve the behavior of ADHD patients. Other notable findings include a significantly lower population of Dialister in unmedicated ADHD, which rose after patients were medicated. A smaller amount of Faecalibacterium were also found in ADHD patients. This may explain the pathogenesis of ADHD, as Faecalibacterium is known for its anti-inflammatory products. It is possible the scarcity of this genera could induce overproduction of pro-inflammatory cytokines, which is in accordance with the high level of pro-inflammatory cytokines found in children with ADHD. CONCLUSION: There were no studies that examined which bacterial taxa correlated most to ADHD. This might occur due to the different model and methods in each study. Further study is needed to identify the correlation between gut microbiota and ADHD.