Safety and efficacy of favipiravir for the management of COVID-19 patients: A preliminary randomized control trial.

Background: The novel coronavirus disease, commonly called COVID-19, has already killed millions of lives. Our study aimed to identify a safe and right drug for the management of such globally threatened COVID-19. Methods: This preliminary double-blinded randomized controlled trial was done among 57 hospitalized COVID-19 patients in the early stage of their illness. Of them, 29 patients received Favipiravir (FVP) and the remaining 28 patients received a placebo under the standard of care. Among the patients, 4 from Favipiravir (FVP) group and 3 from the placebo group were discontinued. The patients were observed regularly for a period of 10 days. Result: In our study, the FVP treated group showed accelerated viral clearance compared to the placebo-treated group. Assessment of chest X-ray showed remarkable improvement of pheumonia patient in group A compared to Group B. Hematological and Biochemical parameters such as total WBC count, neutrophil and lymphocyte counts were examined. No significant differences in the hematological parameters such as WBC count, neutrophil and lymphocyte counts in Group A and Group B patients. Liver transaminases levels were also stable in FVP treated group (average ALT ranges 39.4-46.2; AST 28.2-32.8). Conclusion: The drug Favipiravir displayed remarkable improvements in the clinical conditions and recovery of COVID-19 patients at the early stages of their infections.

The polymorphic landscape analysis of GATA1 exons uncovered the genetic variants associated with higher thrombocytopenia in dengue patients.

The current study elucidated an association between gene variants and thrombocytopenia through the investigation of the exonic polymorphic landscape of hematopoietic transcription factor-GATA1 gene in dengue patients. A total of 115 unrelated dengue patients with dengue fever (DF) (N = 91) and dengue hemorrhagic fever (DHF) (N = 24) were included in the study. All dengue patients were confirmed through detection of NS1 antigen, IgM, and IgG antibodies against the dengue virus. Polymerase chain reaction using specific primers amplified the exonic regions of GATA1 while Sanger sequencing and chromatogram analyses facilitated the identification of variants. Variants G>A (at chX: 48792009) and C>A (at chX: 4879118) had higher frequency out of 13 variants identified (3 annotated and 10 newly recognized). Patients carrying either nonsynonymous or synonymous variants had significantly lower mean values of platelets compared to those harboring the reference nucleotides (NC_000023.11). Further analyses revealed that the change in amino acid residue leads to the altered three-dimensional structure followed by interaction with neighboring residues. Increased stability of the protein due to substitution of serine by asparagine (S129N at chX: 48792009) may cause increased rigidity followed by reduced structural flexibility which may ultimately disturb the dimerization (an important prerequisite for GATA1 to perform its biological activity) process of the GATA1 protein. This, in turn, may affect the function of GATA1 followed by impaired production of mature platelets which may be reflected by the lower platelet counts in individuals with such variation. In summary, we have identified new variants within the GATA1 gene which were found to be clinically relevant to the outcome of dengue patients and thus, have the potential as candidate biomarkers for the determination of severity and prognosis of thrombocytopenia caused by dengue virus. However, further validation of this study in a large number of dengue patients is warranted. Trial Registration: number SLCTR/2019/037.

Antibody Response to ChAdOx1-nCoV-19 Vaccine Among Recipients in Bangladesh: A Prospective Observational Study.

PURPOSE: The aim of the study was to assess the antibody response to the ChAdOx1-nCoV vaccine in individuals who were not previously infected by COVID-19. PATIENTS AND METHODS: All people aged 18-65 years who received their first vaccination with ChAdOx1-nCoV from March to May 2021 were approached for inclusion. Individuals with sufficient antibody titers against SARS-CoV-2 infection before vaccination were considered previously infected and were excluded from the analysis. We observed viral spike protein RBD-S1-specific IgG antibody levels at day 28 of the first dose of vaccination and day 14 of the second dose of vaccination (74 days from index vaccination). An optical density ratio (ODR) of >1.1 was considered to have a positive antibody response, 0.8 to 1.1 borderline and <0.8 was denoted as negative. Informed consent was ensured before enrollment, and ethical principles conformed with the current Declaration of Helsinki. RESULTS: This observational study comprised 769 infection-naïve individuals (mean age 40.5 years, 38.9% female). Spike-specific IgG antibody responses elicited after the first and second doses of vaccine were 99.9% and 100%, respectively. The median ODR was 5.43 (interquartile range [IQR]: 4.32-6.98) and 10.90 (IQR 9.02-11.90) after the first and second doses. Higher age was associated with lower antibody levels after both dosages. However, no sex-specific variation was seen. People with comorbidity had a lower antibody level after the second dose. Tenderness (51.46%) and fever (19.30%) were the most common local and systemic side effects after vaccination. CONCLUSION: This study was one of the earlier attempts in the country to assess the antibody response to ChAdOx1-nCoV vaccine recipients. The results imply that general people should be encouraged to take the vaccine at their earliest.

A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness.

Ivermectin, a US Food and Drug Administration-approved anti-parasitic agent, was found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. A randomized, double-blind, placebo-controlled trial was conducted to determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients. The trial included 72 hospitalized patients in Dhaka, Bangladesh, who were assigned to one of three groups: oral ivermectin alone (12 mg once daily for 5 days), oral ivermectin in combination with doxycycline (12 mg ivermectin single dose and 200 mg doxycycline on day 1, followed by 100 mg every 12 h for the next 4 days), and a placebo control group. Clinical symptoms of fever, cough, and sore throat were comparable among the three groups. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). There were no severe adverse drug events recorded in the study. A 5-day course of ivermectin was found to be safe and effective in treating adult patients with mild COVID-19. Larger trials will be needed to confirm these preliminary findings.

Investigation of the efficacy and safety of eltrombopag to correct thrombocytopenia in moderate to severe dengue patients - a phase II randomized controlled clinical trial.

BACKGROUND: The dengue-infected patients with or without hemorrhagic manifestations, typically exhibit moderate to severe thrombocytopenia. A thrombopoietin receptor agonist - eltrombopag has been efficacious in correcting thrombocytopenia in patients with various pathological conditions including immune thrombocytopenia, chronic liver disease, and severe aplastic anemia. This study investigated the efficacy and safety of eltrombopag to correct dengue-mediated thrombocytopenia. METHODS: In this open-label, randomized controlled phase-II trial, patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) having platelet (PLT) count lower than 100 × 109/L without comorbidity, pregnancy, and liver abnormalities were enrolled in Dhaka Medical College Hospital, Better Life Hospital and AMZ hospital, Dhaka, Bangladesh. Between October 10, 2019, and December 30, 2019, 123 DF and DHF patients were assessed for eligibility to be enrolled in the trial. Fourteen patients were excluded as they failed to fulfill the inclusion criteria (N = 6) or refused to participate in the trial (N = 8). Finally, 109 patients were randomly assigned to either Group 1, (N = 36), Group 2 (N = 37), or Control-group (N = 36) in a 1:1:1 ratio. Two doses of eltrombopag - 25 mg/day and 50 mg/day were administered to Group-1 and Group-2 patients, respectively whereas the control-group patients received standard dengue treatment without eltrombopag. The management of all enrolled patients was according to WHO guidelines. The randomization procedure was performed by using a computerized system (STATA Inc.). CBC and immature platelet fraction (IPF) were monitored from Day-0 to Day-7. Absolute immature platelet count (A-IPC) was calculated from PLT count and IPF for each patient. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured on Day-0 and Day-4 and an Ultrasonogram (USG) of the abdomen was performed on Day-4 and Day-7 for each patient. The efficacy of eltrombopag as the primary outcome of the trial was investigated by the proportion of patients with recovered platelet count receiving eltrombopag with corrected platelet count (platelet count above the lower normal limit: 150 × 109/L) on Day-7 of the enrollment as compared to the Control-group. As the secondary outcomes, the reduction of bleeding tendency in response to eltrombopag as well as the safety of eltrombopag in dengue patients were assessed. The safety was evaluated in case of adverse events, liver function enzymes AST/ALT levels and USG. This trial is registered with the international clinical trial registry, number SLCTR/2019/037. RESULTS: A total of 101 patients including 77 DF and 24 DHF patients completed the trial as eight patients left the trial without completing the follow-up. Patients of the different groups were compared with respect to mean age (26±8, 30±10 and 30±9 years for, Group-1,-2 and Control-group, respectively) (p-value= 0.23) and basal PLT count (Group-1: 58±24 × 109; Group-2: 52±29 × 109 and control-group: 55±30 × 109) (p-value= 0.63). The mean PLT counts for Group-1 (332 × 109/L ± 92) and Group-2 (371 × 109/L ± 111) were significantly higher than control-group (194 × 109/L ± 96) on Day-7 (adjusted p-value= 1.15 × 10-06 for Group-1 vs. Control-group, and adjusted p-value= 1.82 × 10-08 for Group-2 vs. Control-group).). On Day-7, 91% of Group-1 (N = 30) and Group-2 (N = 32) patients who received eltrombopag achieved primary endpoint of PLT count above than lower normal limit (150 × 109/L) (Group-1: 91%, OR: 8.33, 95% CI: 2.11 to 32.80, p-value: 0.0024 and Group-2: 91%, OR: 8.89, 95% CI: 2.26 to 34.89, p-value: 0.0017) compared to 55% (N = 18) of control-group patients who did not receive eltrombopag. The bleeding manifestations for thirteen out of fourteen grade-II DHF patients were subsided within Day-7 who received eltrombopag, whereas four out of ten grade-II DHF patients with PLT counts lower than the lower normal limit in the control group showed intermittent bleeding symptoms throughout the trial period. Mean A-IPC but not IPF was significantly higher for eltrombopag-treated groups in comparison to the Control-group. The frequency of the most common adverse events (vomiting and diarrheal tendencies) was similar in the treated-and control-groups (N = 5, 15%, and N = 3, 9% for Group-1 and -2, respectively vs. N = 4, 12% in the Control-group). Ten (30%) patients of Group-1 and, fourteen (40%) patients of Group-2 showed increased AST (U/L) as opposed to nine patients (27%) in the Control-group. Increased ALT levels were observed for three (9%), nine (26%), and seven (21%) patients belonging to the Group-1, -2, and Control-group, respectively. PLT counts higher than the upper normal limit (450 × 109/L) on Day-7 were observed for seven patients who were administered the higher dose (50 mg/day) in contrast to the three patients receiving the lower dose (25 mg/day). USG reports did not show thrombosis events in any of the patients. INTERPRETATION: The trial revealed that the administration of eltrombopag in a short regimen for three days was efficacious to restore the PLT count in DF and DHF patients. The higher number of A-IPCs in eltrombopag treated patients underscored the possible mode of action of eltrombopag through stimulating megakaryopoiesis in dengue patients. The trial hints toward the positive effect of eltrombopag in the cessation of bleeding manifestation. Administration of the lower dose (25 mg/day) of eltrombopag was shown to be safer and equally efficacious to the higher dose (50 mg/day) in treating dengue-infected patients.

Hepatitis C virus treatment in people who inject drugs (PWID) in Bangladesh.

BACKGROUND: Given the considerable social marginalization experienced by people who inject drugs (PWID), treatment of hepatitis C virus (HCV) in this population presents unique challenges. This study assessed the feasibility of treating HCV infection with direct-acting antiviral (DAA) medications among PWID receiving harm reduction services from a Drop-in-Center in Dhaka, Bangladesh. METHODS: In this prospective study conducted between December 2016 and May 2018, 200 PWID with either recent injecting drug use (i.e., within the previous two months) or a history of injecting drug use and are currently receiving opioid substitution therapy were recruited. Blood was collected to conduct relevant laboratory tests. Eligible PWID who tested positive for HCV RNA (n = 55), were provided daily daclatasvir (60 mg) and sofosbuvir (400 mg) for 12 weeks after which adherence level, sustained virologic response (SVR), and reinfection were assessed. RESULTS: At baseline, 40% (n = 79) of the 200 participants recruited to the study tested positive for antibodies to HCV and 34% (n = 68) had detectable HCV RNA in their blood. Of 55 eligible PWID who initiated treatment, 93% (n = 51) completed treatment while 87% (n = 48) were available for follow-up SVR assessment, all of whom achieved SVR. Thus, intent-to-treat SVR was 87% and the modified intent-to-treat SVR was 100% with one reinfection (4•2 cases per 100 person-years). Further, 75% (i.e., 41 out of the 55 participants) were at least 90% adherent to therapy. CONCLUSION: Our findings strongly suggest that HCV treatment using sofosbuvir+daclatasvir for PWID enrolled in existing harm reduction programs in Bangladesh is feasible but may require additional interventions such as Opioid Substitution Therapy, intense follow up by outreach workers, and services and counselling provided by full time clinicians.