Increased risk of early-onset preeclampsia in pregnant women with COVID-19.

OBJECTIVE: To estimate incidence, risk of early and late-onset preeclampsia (PE) and understand their relationship with severity of COVID-19. METHODS: Pregnant women with COVID-19 (n = 1929) were enrolled from 1 April 2020 to 24 February 2022. Primary outcome measure was incidence and risk of early onset PE in women with COVID-19. RESULTS: The incidence of early and late-onset PE was 11.4% and 5.6%. Moderate to severe COVID-19 was associated with eight times higher risk of early onset PE [aOR = 8.13 (1.56-42.46), p = 0.0129] compared to asymptomatic group. CONCLUSIONS: Risk of early onset PE was higher in pregnant women with symptomatic COVID-19 as compared to asymptomatic women.

Outcomes in neonates born to mothers with COVID-19 during the second wave in India.

COVID-19 pandemic has affected all age groups globally including pregnant women and their neonates. The aim of the study was to understand outcomes in neonates of mothers with COVID-19 during the first and second waves of COVID-19 pandemic. A retrospective analysis of 2524 neonates born to SARS-CoV-2-infected mothers was conducted during the first wave (n = 1782) and second wave (n = 742) of the COVID-19 pandemic at five study sites of the PregCovid registry in Maharashtra, India. A significant difference was noted in preterm birth, which was higher in the second wave (15.0%, 111/742) compared to the first wave (7.8%, 139/1782) (P < 0.001). The proportion of neonates requiring NICU admission was significantly higher in the second wave (19.0%, 141/742) as compared to that in the first wave (14.8%, 264/1782) (P < 0.05). On comparing regional differences, significantly higher neonatal complications were reported from Mumbai metropolitan region (P < 0.05). During the second wave of COVID-19, birth asphyxia and prematurity were 3.8- and 2.1-fold higher respectively (P < 0.001). Neonatal resuscitation at birth was significantly higher in second wave (3.4%, 25/742 vs 1.8%, 32/1782) (P < 0.05). The prevalence of SARS-CoV-2 infection in neonates was comparable (4.2% vs 4.6%) with no significant difference between the two waves. CONCLUSION: Higher incidence of adverse outcomes in neonates born to SARS-CoV-2-infected mothers in the second wave of COVID-19 as compared to the first wave. TRIAL REGISTRATION: PregCovid study is registered with the Clinical Trial Registry of India (CTRI/2020/05/025423, Registered on 28/05/2020). WHAT IS KNOWN: • The second wave of COVID-19 was more lethal to pregnant women than the first wave. Newborns are at risk of developing complications. WHAT IS NEW: • Birth asphyxia, prematurity, and neonatal resuscitation at birth were significantly higher in the second wave as compared to those in the first wave of the COVID-19 pandemic in India.

Clinical presentation, pregnancy complications, and outcomes of pregnant women with COVID-19 during the Omicron-dominant third wave in Mumbai, India.

OBJECTIVE: To study clinical presentation, disease severity, pregnancy complications, and maternal outcomes in women affected with coronavirus disease 2019 (COVID-19) during the third wave compared with the first and second waves of COVID-19. METHODS: A retrospective, observational cohort study was conducted among 2058 pregnant and postpartum women with COVID-19 admitted during three wave periods at a tertiary care COVID-19-dedicated hospital. RESULTS: The number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -infected pregnant and postpartum women with symptoms of COVID-19 was four times higher during the third wave compared with the first (odds ratio [OR] 4.6, 95% confidence interval [CI] 3.5-6.0, P < 0.001). There was a significantly lower proportion of pregnant and postpartum women with moderate to severe COVID-19 during the third wave (0.6%, 2/318) compared with those during the first wave (2.4%, 27/1143, P < 0.001) and second wave (14.4%, 86/597, P < 0.001). The intensive care/high dependency unit admissions during the third wave were significantly lower (2.5%, 8/318) than during the second wave (14.7%, 88/597; OR 0.2, 95% CI 0.1-0.3, P < 0.001) but similar to the first wave (2.4%, 27/1143). CONCLUSIONS: Decreased severity of COVID-19, reduced maternal mortality, and morbidity were reported in the third wave compared with the first wave and second wave of COVID-19 in the Mumbai Metropolitan Region, India. TRIAL REGISTRATION: The study is registered with the Clinical Trial Registry of India (Registration no: CTRI/2020/05/025423).

Increased spontaneous preterm births during the second wave of the coronavirus disease 2019 pandemic in India.

OBJECTIVE: To compare spontaneous preterm birth (SPTB) and iatrogenic preterm birth (IPTB) rates during both waves of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Retrospective analysis of the PregCovid registry of pregnant women with COVID-19 was performed at a dedicated COVID-19 hospital in Mumbai, India. The data of 1630 women were analyzed for this study between April 4, 2020 and July 4, 2021. Prepandemic data were analyzed and compared with pandemic data. Main outcome measure was spontaneous preterm birth rate. RESULTS: Preterm deliveries were higher during the second wave (46/329; 14%) compared with the first wave (82/807; 10.2%) of the COVID-19 pandemic (P = 0.065). Higher SPTBs were reported during the second wave than the first wave (12.5% versus 8.3%) (P = 0.03) as well as the prepandemic period (12.5% versus 10.5%) (P = 0.286). IPTBs were significantly lower in the pandemic period than in the prepandemic period (1.8 versus 3.3) (P = 0.012). CONCLUSION: In Mumbai, India, we found an unusual change in SPTBs during the 6 months of the second wave of COVID-19 compared with the previous 10 months of the first wave of pandemic and 1 year of prepandemic.

Protocol for a prospective, hospital-based registry of pregnant women with SARS-CoV-2 infection in India: PregCovid Registry study.

INTRODUCTION: Pregnant women are at increased risk of contracting COVID-19 due to several factors and therefore require special attention. However, the consequences of the COVID-19 pandemic on pregnant women and their newborns remain uncharted. The PregCovid registry aims to document the impact of SARS-CoV-2 infection on pregnant, postpartum women and their newborns. The aim of the registry is also to determine mother-to-child transmission of SARS-CoV-2 infection in India. METHODS AND ANALYSIS: PregCovid is a hospital-based registry for capturing information of pregnant, postpartum women with COVID-19 and their newborns in India. Medical case records of pregnant and postpartum women with a laboratory-confirmed diagnosis of COVID-19 will be captured in real-time using an online electronic patient record software. The data analysis will be carried out for symptoms, the severity of COVID-19, pregnancy complications, maternal morbidity and mortality, neonatal complications, mother-to-child transmission, etc. Data analysis will be carried out for different waves of the COVID-19 pandemic for rapid response and developing strategies well in advance to manage pregnant women infected with SARS-CoV-2. The evidence generated from the registry will be regularly shared with the appropriate authorities for policy decisions. Thus, the registry data may be useful for planning the strategies for better management of pregnant women with COVID-19. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Ethics Committees of all the participating study sites under the Medical Education and Drugs Department, Government of Maharashtra, Topiwala National Medical College & BYL Nair Charitable Hospital, Mumbai and ICMR-National Institute for Research in Reproductive and Child Health, Mumbai, India. The results from this study will be disseminated with local, state, and national health authorities, collaborators and the general population on the study website (https://pregcovid.com) as well as dissemination through scientific meetings and publications. TRIAL REGISTRATION NUMBER: CTRI/2020/05/025423.

Opposing roles for sMAdCAM and IL-15 in COVID-19 associated cellular immune pathology.

Immune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study, we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM), and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n = 130) at various stages of disease progression together with healthy controls (n = 16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells, were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, plasma IL-15 levels negatively correlated with T, B, and NK count suggesting a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with a longer duration of hospitalization.

Clinical characteristics, outcomes, & mortality in pregnant women with COVID-19 in Maharashtra, India: Results from PregCovid registry.

Background & objectives: The PregCovid registry was established to document the clinical presentations, pregnancy outcomes and mortality of pregnant and post-partum women with COVID-19. Methods: The PregCovid registry prospectively collects information in near-real time on pregnant and post-partum women with a laboratory-confirmed diagnosis of SARS-CoV-2 from 19 medical colleges across the State of Maharashtra, India. Data of 4203 pregnant women collected during the first wave of the COVID-19 pandemic (March 2020-January 2021) was analyzed. Results: There were 3213 live births, 77 miscarriages and 834 undelivered pregnancies. The proportion of pregnancy/foetal loss including stillbirths was six per cent. Five hundred and thirty-four women (13%) were symptomatic, of which 382 (72%) had mild, 112 (21%) had moderate, and 40 (7.5%) had severe disease. The most common complication was preterm delivery (528, 16.3%) and hypertensive disorders in pregnancy (328, 10.1%). A total of 158 (3.8%) pregnant and post-partum women required intensive care, of which 152 (96%) were due to COVID-19 related complications. The overall case fatality rate (CFR) in pregnant and post-partum women with COVID-19 was 0.8 per cent (34/4203). Higher CFR was observed in Pune (9/853, 1.1%), Marathwada (4/351, 1.1%) regions as compared to Vidarbha (9/1155, 0.8%), Mumbai Metropolitan (11/1684, 0.7%), and Khandesh (1/160, 0.6%) regions. Comorbidities of anaemia, tuberculosis and diabetes mellitus were associated with maternal deaths. Interpretation & conclusions: The study demonstrates the adverse outcomes including severe COVID-19 disease, pregnancy loss and maternal death in women with COVID-19 in Maharashtra, India.

sMAdCAM: IL-6 Ratio Influences Disease Progression and Anti-Viral Responses in SARS-CoV-2 Infection.

The role of sMAdCAM, an important gut immune migratory marker, remains unexplored in COVID-19 pathogenesis considering recent studies positing the gut as a sanctuary site for SARS-CoV-2 persistence. Thus, assimilating profiles of systemic inflammatory mediators with sMAdCAM levels may provide insights into the progression of COVID-19 disease. Also, the role of these markers in governing virus specific immunity following infection remains largely unexplored. A cohort (n = 84) of SARS-C0V-2 infected individuals included a group of in-patients (n = 60) at various stages of disease progression together with convalescent individuals (n = 24) recruited between April and June 2020 from Mumbai, India. Follow-up of 35 in-patients at day 7 post diagnosis was carried out. Th1/Th2/Th17 cytokines along with soluble MAdCAM (sMAdCAM) levels in plasma were measured. Also, anti-viral humoral response as measured by rapid antibody test (IgG, IgM), Chemiluminescent Immunoassay (IgG), and antibodies binding to SARS-CoV-2 proteins were measured by Surface Plasmon Resonance (SPR) from plasma. IL-6 and sMAdCAM levels among in-patients inversely correlated with one another. When expressed as a novel integrated marker-sMIL index (sMAdCAM/IL-6 ratio)-these levels were incrementally and significantly higher in various disease states with convalescents exhibiting the highest values. Importantly, sMAdCAM levels as well as sMIL index (fold change) correlated with peak association response units of receptor binding domain and fold change in binding to spike respectively as measured by SPR. Our results highlight key systemic and gut homing parameters that need to be monitored and investigated further to optimally guide therapeutic and prophylactic interventions for COVID-19.

A novel ORF1a-based SARS-CoV-2 RT-PCR assay to resolve inconclusive samples.

BACKGROUND: India bears the second largest burden of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. A multitude of reverse transcription polymerase chain reaction (RT-PCR) detection assays with disparate gene targets, including automated high-throughput platforms, are available. Varying concordance and interpretation of diagnostic results in this setting can result in significant reporting delays, leading to suboptimal disease management. This article reports the development of a novel ORF1a-based SARS-CoV-2 RT-PCR assay - Viroselect - that shows high concordance with conventional assays and the ability to resolve inconclusive results generated during the peak of the epidemic in Mumbai, India. METHODS: A unique target region within SARS-CoV-2 ORF1a - the non-structural protein 3 (nsp3) region - was used to design and develop the assay. This hypervariable region (1923-3956) between SARS-CoV-2, SARS-CoV-1 and Middle East respiratory syndrome coronavirus was utilized to design the primers and probes for the RT-PCR assay. The concordance of this assay with commonly used emergency use authorization (US Food and Drug Administration) manual kits and an automated high-throughput testing platform was evaluated. Further, a retrospective analysis was carried out using Viroselect on samples reported as 'inconclusive' between April and October 2020. RESULTS: In total, 701 samples were tested. Concordance analysis of 477 samples demonstrated high overall agreement of Viroselect with both manual (87.6%) and automated (84.7%) assays. Also, in the retrospective analysis of 224 additional samples reported as 'inconclusive', Viroselect was able to resolve 100% (19/19) and 93.7% (192/205) of samples which had inconclusive results on manual and automated high-throughput platforms, respectively. CONCLUSION: Viroselect had high concordance with conventional assays, both manual and automated, and has potential to resolve inconclusive samples.

Differential impact of COVID-19 in pregnant women from high-income countries and low- to middle-income countries: A systematic review and meta-analysis.

BACKGROUND: SARS-CoV-2 has infected a large number of pregnant women. OBJECTIVE: To compare clinical, perinatal outcomes of women with COVID-19 from high-income countries (HICs) and low- to middle-income countries (LMICs). SEARCH STRATEGY: Online databases were searched. SELECTION CRITERIA: Original studies on pregnant women with COVID-19 were included. DATA COLLECTION AND ANALYSIS: Information on clinical presentation, co-morbidities, pregnancy outcomes, neonatal outcomes, and SARS-CoV-2 infection in neonates was extracted. MAIN RESULTS: The pooled estimate of SARS-CoV-2 positive neonates is 3.7%. Symptomatic presentations are less common in LMICs compared to HICs (odds ratio [OR] 0.38). Diabetes (OR 0.5), hypertension (OR 0.5), and asthma (OR 0.14) are commonly reported from HICs; hypothyroidism (OR 2.2), anemia (OR 3.2), and co-infections (OR 6.0) are commonly reported in LMICs. The overall risk of adverse pregnancy outcomes is higher in LMICs compared to HICs (OR 2.4). Abortion (OR 6.2), stillbirths (OR 2.0), and maternal death (OR 7.8) are more common in LMICs. Preterm births and premature rupture of membranes are comparable in both groups. Neonatal deaths (OR 3.7), pneumonia (OR 7.5), and neonatal SARS-CoV-2 infection (OR 1.8) are commonly reported in LMICs. CONCLUSIONS: In LMICs, pregnant women and neonates are more vulnerable to adverse outcomes due to COVID-19. PROSPERO registration no: CRD42020198743.

Clinical Characteristics, Management, and Short-Term Outcome of Neonates Born to Mothers with COVID-19 in a Tertiary Care Hospital in India.

INTRODUCTION: We describe the clinical characteristics, management, and short-term outcomes of SARS-CoV-2 neonates born to mothers with COVID-19 in a tertiary care hospital in Mumbai, India. METHODS: The study is a retrospective analysis of 524 neonates born to mothers with COVID-19 admitted from 14th April 2020 to 31st July 2020. RESULTS: SARS-CoV-2 infection was detected in 6.3% of the newborns of the mothers with COVID-19. No significant differences were observed between maturity at gestation, birth weight and sex of SARS-CoV-2 infected and noninfected newborns. The risk of sepsis was 4.09 [95% confidence interval (95% CI) 1.28-13.00] fold higher in the neonates with SARS-CoV-2 as compared to the noninfected group (p = 0.031). Poor feeding was significantly more common among SARS-CoV-2 infected neonates (12.1%) as compared to the noninfected neonates (2.7%) (p = 0.017). There was a total of 13 neonatal deaths, of which 3 deaths occurred in SARS-CoV-2 infected neonates (9%) while 10 (2.04%) in the SAR-CoV-2 negative group. The risk of neonatal death was higher in SARS-CoV-2 infected newborns [odds ratio (OR) 4.8; 95% CI 1.25-18.36]. CONCLUSION: Neonatal SARS-CoV-2 infection is observed in almost 6% of neonates born to mothers with perinatal COVID-19. There is a higher risk of adverse outcomes such as neonatal sepsis and death in the SARS-CoV-2 infected as compared to the noninfected neonates.

The current pandemic of COVID-19 has affected all the countries globally. However, the adverse impact of the pandemic is more seen in the low-income and middle-income countries (LMICs). Although there is evidence on the adverse impact of the SARS-CoV-2 on the health of mothers and neonates, the evidence is mainly from high-income countries. For reducing the mortality and morbidity due to COVID-19 in LMICs, there is a need to generate evidence from the LMICs. The present study is a part of the National Registry of pregnant women with COVID-19 in India (PregCovid registry). Our study demonstrates a higher risk of adverse outcomes such as neonatal sepsis and death in the SARS-CoV-2 infected as compared to the noninfected neonates. The study also showed the risk of SARS-CoV-2 infection in 6.3% of neonates born to mothers with COVID-19.

A retrospective analysis of COVID-19 diagnosis results obtained by rapid antigen tests and RT-PCR: Implications for disease management.

There is a need for understanding and establishment of the most appropriate testing algorithm for COVID-19 diagnosis in asymptomatic high-risk groups. Here, we present a retrospective analysis of RT-PCR results obtained from 412 cases tested negative for coronavirus disease 2019 (COVID-19) by rapid antigen testing method. Among 178 (43.2%) asymptomatic individuals, 44.9% of the high risk contacts, 12.2% of police custody individuals, 22.22% of the pregnant women and 33.33% of individuals hospitalised for preoperative or other medical conditions showed RT-PCR positivity. Our results suggest a need for focussed and intensive (multi-modality) testing in groups at high risk for SARS-CoV-2 infection.

Detection of SARS-CoV-2 infection by RT-PCR test: factors influencing interpretation of results.

In this current pandemic of coronavirus disease 2019 (COVID-19), prompt interventions in terms of early detection and clinical management along with isolation of positive cases is of utmost importance. This helps to limit not only the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections but also the morbidity and mortality associated with it. Different strategies for screening of COVID-19 in containment zones and non-containment areas include testing of symptomatic patients and their contacts in fever clinics, hospital-based testing, testing on demand and population-based screening. The choice of tests like reverse-transcription polymerase chain reaction (RT-PCR), rapid antigen testing (RAT) or antibody test depends upon these strategies and also the turnaround time. Currently, RT-PCR is considered the gold standard for COVID-19 detection. This commentary provides the insights and experiences on COVID-19 diagnosis by RT-PCR. The utility of this test is limited by several false positive, false negative and inconclusive results at early stages of infection, scarcity of reagents and lack of well-equipped labs including trained staff. Moreover, appropriate sample collection and transport, standard laboratory protocols, stringent quality control norms, good quality RNA extraction kits, PCR kits with suitable primers can help in improving accuracy of the test results. A careful assessment of clinical, radiological and molecular findings is required for identifying potential cases of COVID-19.

An overview of preclinical animal models for SARS-CoV-2 pathogenicity.

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of fatalities globally since its origin in November 2019. The SARS-CoV-2 shares 79 and 50 per cent genome similarity with its predecessors, severe SARS-CoV and Middle East respiratory syndrome (MERS) coronavirus, all belonging to the same genus, Betacoronavirus. This relatively new virus has stymied the effective control of COVID-19 pandemic and caused huge social and economic impact worldwide. The FDA-approved drugs were re-purposed to reduce the number of fatalities caused by SARS-CoV-2. However, controversy surrounds about the efficacy of these re-purposed antiviral drugs against SARS-CoV-2.This necessitates the identification of new drug targets for SARS-CoV-2. Hence, the development of pre-clinical animal model is warranted. Such animal models may help us gain better understanding of the pathophysiology of SARS-CoV-2 infection and will be effective tools for the evaluation and licensure of therapeutic strategies against SARS-CoV-2. This review provides a summary of the attempts made till to develop a suitable animal model to understand pathophysiology and effectiveness of therapeutic agents against SARS-CoV-2.