COVID-19 Antibodies as Predictor of Severe Dengue among Hospitalized Children with Dengue Illness in the Post-third-wave Period of COVID-19 Infection in India.

BACKGROUND: There were widespread unconfirmed reports about the increased severity of dengue post-second wave of the COVID-19 pandemic in India. It is known that a second dengue infection with a different strain in an individual can trigger antibody-dependent enhancement (ADE). A similar phenomenon is hypothesized for severe COVID-19 infection since both dengue and COVID-19 are viral diseases with different and varying strains. However, much research is needed to confirm this hypothesis. In this context, we intended to assess the severity of dengue illness in relation to previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, possibly the role of COVID-19 antibodies as an early predictor of severe dengue illness. OBJECTIVE: To assess the utility of COVID-19 antibodies for early identification of severe dengue illness among children in the post-third-wave period of COVID-19 infection in India. MATERIALS AND METHODS: All hospitalized children with dengue illness were categorized as severe (shock and/or hemorrhage and/or multi-organ dysfunction) and non-severe dengue illness (dengue with or without warning signs) as per WHO definition. COVID-19 antibody titers were estimated in both groups. Clinical features and seroprevalence of COVID-19 antibodies were compared in both groups. RESULT: A total of 31 children were studied (13 severe and 18 non-severe dengue illnesses). The most common symptoms prior to presenting to the hospital included fever (100% in both groups), vomiting (85% in severe and 63% in non-severe), abdominal pain (85% in severe and 50% in non-severe), poor feeding (54% in severe and 28% in non-severe), and skin rashes (15% in severe and none in non-severe). The mean duration from the onset of fever to the first hospital visit was 4.6 days in severe illness and 5.3 days in non-severe dengue illness. The mean duration of hospitalization was 9.7 days in severe dengue illness and 4.1 days in non-severe dengue illness. While 92.3% of all severe dengue had significantly higher COVID-19 antibody titers, it was found elevated only in 44.4% of the children with non-severe dengue illness (p-value 0.0059; Yates' corrected p-value 0.0179). CONCLUSION: Clinical symptoms prior to presenting to the hospital were fever, vomiting, abdominal pain, poor oral feeding, and skin rashes. While fever, vomiting, and abdominal pain were seen commonly in both severe and non-severe dengue illnesses, the presence of skin rash during febrile phase is associated with severe dengue illness only. Hospitalized children having severe dengue had increased seroprevalence of COVID-19 antibodies (92.3%) compared to children with non-severe dengue (44.4%). However, there is no corelation of the severity of dengue illness with absolute values of COVID-19 antibody levels. Therefore, the presence of COVID-19 antibodies (previous COVID-19 infection) can be a predictor of severe illness in children with dengue especially if associated with poor oral feeding and skin rashes. The limitation of the study is its lesser sample size to conclude any definitive statement; nevertheless, the study paves way for a similar cohort of a larger sample size to draw conclusions.

Cariprazine, A Dopamine D2/D3 Receptor Partial Agonist, Modulates ABCG2-Mediated Multidrug Resistance in Cancer.

Multidrug resistance (MDR) is a continuing clinical problem that limits the efficacy of chemotherapy in cancer. The over expression of the ATP-binding cassette (ABC) family G2 (ABCG2) transporter is one of the main mechanisms that mediates MDR in cancer. Molecular modeling data indicated that cariprazine, a dopamine D2/D3 receptor partial agonist, had a significant binding affinity for ABCG2 transporter with a Glide XP score of -6.515. Therefore, in this in vitro study, we determined the effect of cariprazine on MDR resulting from the overexpression of ABCG2 transporters. Alone, cariprazine, at concentrations up to 20 µM, did not significantly decrease cell viability. Cariprazine, at concentrations ranging from 1 to 10 µM, did not significantly alter the cytotoxicity of mitoxantrone (MX) in the parental non-small cell cancer cell line, H460 and colon cancer cell S1. However, cariprazine (1⁻20 µM) significantly enhanced the efficacy of ABCG2 substrate antineoplastic drug MX in the ABCG2-overexpressing MDR cell line, H460-MX20 and S1M1-80, by reducing the resistance fold from 28 to 1 and from 93 to 1.33, respectively. Cariprazine, in a concentration-dependent (1⁻20 µM), significantly increased the intracellular accumulation of Rhodamine 123 in S1M1-80. Interestingly, 10 or 20 µM of cariprazine significantly decreased the expression levels of the ABCG2 protein in the colon and lung cancer cell lines, suggesting that cariprazine inhibits both the function and expression of ABCG2 transporters at nontoxic concentrations. Overall, our results suggest that cariprazine, via several distinct mechanisms, can resensitize resistant cancer cells to mitoxantrone.