A novel metric-based approach of scoring early host immune response from oro-nasopharyngeal swabs predicts COVID-19 outcome.

Unpredictable fatal outcome of COVID-19 is attributed to dysregulated inflammation. Impaired early adaptive immune response leads to late-stage inflammatory outcome. The purpose of this study was to develop biomarkers for early detection of host immune impairment at first diagnosis from leftover RNA samples, which may in turn identify high risk patients. Leftover RNA samples of COVID-19 patients at first diagnosis were stored. Following prospective follow-up, the samples were shorted and categorized into outcome groups. Impaired adaptive T cell response (severity score) and Impaired IL-10 response (undetectable IL-10 in the presence of high expression of a representative interferon response gene) were determined by RT-PCR based assay. We demonstrate that a T cell response based 'severity score' comprising rational combination of Ct values of a target genes' signature can predict high risk noncomorbid potentially critical COVID-19 patients with a sensitivity of 91% (95% CI 58.7-99.8) and specificity of 92.6% (95% CI 75.7-99) (AUC:0.88). Although inclusion of comorbid patients reduced sensitivity to 77% (95% CI 54.6-92.2), the specificity was still 94% (95% CI 79.8-99.3) (AUC:0.82). The same for 'impaired IL-10 response' were little lower to predict high risk noncomorbid patients 64.2% (95% CI 35.1-87.2) and 82% (95% CI 65.5-93.2) respectively. Inclusion of comorbid patients drastically reduce sensitivity and specificity51.6% (95% CI 33.1-69.8) and 80.5% (95% CI 64.0-91.8) respectively. As best of our knowledge this is the first demonstration of a metric-based approach showing the 'severity score' as an indicator of early adoptive immune response, could be used as predictor of severe COVID-19 outcome at the time of first diagnosis using the same leftover swab RNA. The work flow could reduce expenditure and reporting time of the prognostic test for an earliest clinical decision ensuring possibility of early rational management.

Maternal and Neonatal Outcomes Associated With COVID-19 Infection in Pregnant Mothers Admitted in Tertiary Care Hospital in Central State of India.

In spite of various reports on perinatal outcomes of coronavirus disease 2019 (COVID-19) during pregnancies, the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on unborn babies and pregnant mothers are still mysterious. The goal of our research is to examine the perceived fetomaternal outcomes of COVID-19 during pregnancy. A total of 396 pregnant women were admitted to the Department of Gynaecology and Obstetrics, Pt. JNM Medical College, Raipur, Chhattisgarh, India, during the period from July 20, 2020 to January 6, 2021. The presence of SARS-CoV-2 in different biological samples was recorded via positive quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) test results. All the newborns delivered from the infected pregnant mothers were tested as RT-PCR negative. Negative findings of RT-PCR for respiratory swabs of newborns, amniotic fluid, placental tissue, breast milk, vaginal swabs, and cord blood indicated no transmission of the virus from mother to baby. However, maternal outcomes, such as hospitalization (46.96%), preeclampsia (13.88%), pre-term birth (14.39%), prelabor rupture of membranes (PROM) before 34 weeks (3.78%), PROM before 37 weeks (2.77%), vaginal bleeding (4.29%), postpartum hemorrhage (2.52%), pregnancy-induced hypertension (1.51%), and neonatal outcomes such as low birth weight ≤1.5 kg (6.59) and 1.6-2.4 kg (39.34%), intrauterine deaths (IUD) (0.50%), fetal distress (22.33%), NICU admission (5.58%), meconium-stained liquor (14.46%), diarrhea (0.25%), and low APGAR score 4-6 at 1 min (20.54%), were observed. The results of the present study indicate that SARS-CoV-2-induced complications during pregnancy must be taken seriously. Intrauterine fetal deaths occurred at lower rates. There is no substantial proof of vertical perinatal transmission of the virus, as none of the neonates had tested positive for COVID-19.

Placental Histopathology in COVID-19-Positive Mothers.

The placenta is a captivating multifunctional organ of fetal origin and plays an essential role during pregnancy by intimately connecting mother and baby. This study explicates placental pathology and information about 25 placentas collected from the mothers infected with novel coronavirus (SARS-COV-2). So far, congenital transmission of SARS-CoV-2 seems to be remarkably uncommon in spite of many cases of COVID-19 during pregnancy. Out of the 25 placental tissue samples collected, none has shown gene expression of SARS-CoV-2 when confirmed by RT-PCR. At the same time, nasal and throat swab samples collected from newborns of SARS-CoV-2-positive mothers correspondingly tested negative by RT-PCR. The shielding properties of placental barriers against viral infections from mothers to newborns remains a mystery. Major histopathological findings have been recorded as choriodecidual tissue with necrosis, intramural fibrin deposition, chorionic villi with fibrosis, and calcification. Moreover, although recent findings are insufficient to prove direct placental transmission of COVID-19, the abundance of angiotensin-converting enzymes-2 (ACE-2) on the placental surface could potentially contribute to unpleasant outcomes during pregnancy as SARSCoV-2 gains access to human cells via ACE-2. Finally, the significance of these findings is vague and needs further study.

Cerebral hemodynamics in children with sickle cell disease in India: An observational cohort study.

India has the second highest number of cases of sickle cell disease (SCD) and affects the most socioeconomically disadvantaged communities living in a horizontal belt from Gujarat to Odisha state. Despite high prevalence, information about cerebral hemodynamics among children with SCD in India remains scarcely described. We performed transcranial Doppler (TCD) to assess cerebral hemodynamics among Indian children with SCD and evaluated their association with clinical and hematological parameters. Children aged 3-18years, diagnosed with SCD living in Raipur in Chhattisgarh and Ahmedabad in Gujarat state were recruited. TCD was performed to obtain flow velocities from middle cerebral (MCA), intracranial internal carotid (ICA) and basilar artery. Associations were evaluated between timed-average-mean-maximum velocities (TAMMV) and various clinical and hematological parameters. Our prospective study included 62 consecutive children with known SCD. Mean ± SD age of the study population was 9.8 ± 3.9 years and 31 (50%) were male. Mean ± SD hemoglobin was 8.64 ± 1.34 Gm/dL while the mean HbSS ± SD was 70.25 ± 15.27%. While 6 (9.6%) children had suffered from stroke during previous 2 years, 7 (11%) demonstrated abnormal TAMMV. Higher HbSS level along with history of iron chelation therapy, blood transfusion and/or stroke showed a trend towards having higher TAMMV. Stroke and cerebral hemodynamic alterations are common among Indian children with SCD. Larger studies with detailed neuroimaging and genetic evaluations are needed for better understanding, characterization, risk stratification as well as optimization of the timing of blood transfusion to reduce physical disabilities among Indian children with SCD.

Proposed Algorithm for Hepatitis E Virus Diagnosis in the Early Phase of Illness.

Hepatitis E virus (HEV), a major etiologic agent of enterically transmitted hepatitis worldwide, is known to cause outbreaks. Diagnosis of the causative agent is important for patient management, understanding epidemiology and outbreak mitigation. We attempted to develop an algorithm for molecular diagnosis and compared the diagnostic accuracy of 2 of HEV IgM ELISA tests during an outbreak. Eighty-four blood samples collected during an outbreak in central India were referred to a nodal laboratory for confirmation of diagnosis. The samples were tested by serological and molecular testes. The results were analyzed by statistical tests. Both the IgM ELISAs were equally competent to diagnose HEV infection when samples were collected after 7.95 ± 3.2 days of onset of illness, whereas nRT-PCR proved a better test when samples were collected between 0 and 6.17 ± 1.97 days of illness. During HEV outbreaks, it is not possible to test all suspected cases by both serological and molecular tests; we suggest testing all ELISA-negative and samples collected in early phase (<7 days) of illness by molecular tests to rule out false-negative results. More studies with large sample size will aid in designing national guidelines for molecular diagnosis of HEV.