RESUMEN
The role of autoantibodies in coronavirus disease (COVID-19) complications is not yet fully understood. The current investigation screened two independent cohorts of 97 COVID-19 patients (Discovery (Disc) cohort from Qatar (n = 49) and Replication (Rep) cohort from New York (n = 48)) utilizing high-throughput KoRectly Expressed (KREX) immunome protein-array technology. Autoantibody responses to 57 proteins were significantly altered in the COVID-19 Disc cohort compared to healthy controls (P [≤] 0.05). The Rep cohort had altered autoantibody responses against 26 proteins compared to non-COVID-19 ICU patients that served as controls. Both cohorts showed substantial similarities (r2 = 0.73) and exhibited higher autoantibodies responses to numerous transcription factors, immunomodulatory proteins, and human disease markers. Analysis of the combined cohorts revealed elevated autoantibody responses against SPANXN4, STK25, ATF4, PRKD2, and CHMP3 proteins in COVID-19 patients. KREX analysis of the specific IgG autoantibody responses indicates that the targeted host proteins are supposedly increased in COVID-19 patients. The autoantigen-autoantibody response was cross-validated for SPANXN4 and STK25 proteins using Uniprot BLASTP and sequence alignment tools. SPANXN4 is essential for spermiogenesis and male fertility, which may predict a potential role for this protein in COVID-19 associated male reproductive tract complications and warrants further research. Significance StatementCoronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, has emerged as a global pandemic with a high morbidity rate and multiorgan complications. It is observed that the host immune system contributes to the varied responses to COVID-19 pathogenesis. Autoantibodies, immune system proteins that mistakenly target the bodys own tissue, may underlie some of this variation. We screened total IgG autoantibody responses against 1,318 human proteins in two COVID-19 patient cohorts. We observed several novel markers in COVID-19 patients that are associated with male fertility, such as sperm protein SPANXN4, STK25, and the apoptotic factor ATF4. Particularly, elevated levels of autoantibodies against the testicular tissue-specific protein SPANXN4 offer significant evidence of anticipating the protein role in COVID-19 associated male reproductive complications.
RESUMEN
Following the COVID-19 pandemic outbreak in late 2019, a large number of antibody tests were developed for use in seroprevalence studies aimed at determining the extent of current or previous SARS-CoV-2 virus infections in a given population. The vast majority of these tests are qualitative and use a single target for antibody detection, incorporating either full-length or truncated versions of the nucleocapsid (N) or spike (S) proteins from SARS-CoV-2. Importantly, mono-epitope tests - whether qualitative or quantitative - are unable to localise antibody binding or characterise the distribution and titres of epitope recognition by anti-SARS-CoV-2 antibodies within an individual or across a population. However, it seems plausible that if such information were available, it may correlate with the presence of potent, high-titre, neutralising antibodies that afford protection again imminent re-infection, as well as with the likelihood of developing a memory B-cell response that would provide more durable protection. We have developed a novel, quantitative, multi-antigen, multiplexed, array-based immunoassay platform, ImmuSAFE COVID+ (ImmuSAFE) comprising 6 functionally validated domains or regions of the N protein of SARS-CoV-2 expressed using Sengenics KREX technology. This array platform enables determination of both the position and breadth of anti-SARS-CoV-2 antibody responses following natural infection or vaccination. To validate our platform, 100 serum samples (confirmed sero-positive COVID-19 cases, n=50; pre-pandemic HIV positive controls, n=50) were tested for IgG seropositivity to the N antigen, yielding 100% specificity and 100% sensitivity. All 50 cases showed positive antibody reactivity towards at least one N protein epitope, whilst all 50 controls showed antibody reactivity below threshold values. Broad variation was also observed in the magnitude and breadth of antibodies present, represented as an Epitope Coverage score (EPC). A positive correlation was observed between increasing age and EPC values, with individuals under 40 years old having a mean EPC score of 3.1, whilst individuals above the age of 60 had a mean EPC of 5.1. This finding may have broad implications for the natural history of COVID-19 disease in different individuals.
RESUMEN
Background: The public health issue of consuming groundwater is a major concern because people often extract groundwater directly from the aquifers either through wells or boreholes without treating it with any form of filtration system or chlorine disinfection. Based on the Malaysian National Drinking Water guidelines the current study was designed to provide a better understanding on the variable factors that are influencing the quality of well-water in an urbanised village in Malaysia. Well water quality assessment of heavy metals, chemicals, microbial and physical parameters were carried out for Sungai Buloh Village in the Klang Valley to ensure it was safe for human consumption. Materials and Methods: Water samples were collected from wells at four sites (Sites A,B,C,D), a river and a tap inside a house in Sungai Buloh village. Soil was sampled from the riverbed and area surrounding the wells. Samples were collected every two months over a one year duration from all sites. The water samples were processed and examined for viruses, coliforms and protozoa as well as for heavy metal contaminants. Results: The turbidity and colour ranged in the average of 0.57-0.13 Nephelometric Turbidity (NTU) and 4.16- 5.00 Total Conjunctive Use (TCU) respectively for all sites except Site C. At Site C the turbidity level was 2.56 ± 1.38 NTU. The well-water was polluted with coliforms (1.2 to 2.4 x 10 3 CFU/100 ml) in all sites, E. coli (0.12 - 4 x 10 2 CFU/100 ml CFU/ 100 ml) and Cryptosporidium oocysts (0.4 cysts/100 ml). All the heavy metals and chemical parameters were within the Malaysian Guidelines’ limits except manganese. The average pH ranged from 5.44 - 6.62 and the temperature was 28 ºC. Conclusion: In summary, the well water at Sungai Buloh is considered unsafe for consumption due to pollution. Therefore the major thrust will be to provide better quality of drinking water to the residents of the village.
