COVID-19 suspicion and diagnosis in pregnancy: A big conundrum!

Introduction: This article aims to discuss all the challenges faced in the diagnosis of coronavirus disease 2019 (COVID-19) in pregnancy, isolation of suspected and positive patients, their management, and the strategies to prevent the transmission of infection among the healthy population and medical fraternity. The diagnosis of COVID in pregnancy is influenced by many factors, including normal physiological changes in pregnancy, comorbid conditions associated with pregnancy, and the presence of asymptomatic infection in patients. Suspicion of COVID-19 in pregnant females is of utmost importance at a primary health center for risk mitigation of exposure to medical personnel. Material and Methods: A retrospective study was carried out in the labour room in a tertiary care center in India. Two groups were made, suspected COVID and confirmed COVID in pregnant patients. The case records were analysed. Results: Out of a total of 5164 admissions, 95 patients were admitted as suspected (1.8%), but only two patients were COVID-positive amongst them. 84% of COVID-positive patients were asymptomatic. Fever was the most common symptom in both groups (P-value: 0.15). Preeclampsia and anaemia were the most common comorbidities in both groups, not statistically significant. There were 32% of intensive acre unit (ICU) admissions in suspected COVID patients, and 77% of them were having respiratory distress. Conclusion: COVID-19 presents as an asymptomatic infection in most pregnant patients. Physiological changes to the cardiorespiratory and immune systems along with associated comorbidities in pregnancy, increase a woman's susceptibility and delay diagnosis. Consideration of patients as suspected COVID at triage stations on the basis of only contact or travel history poses a great burden on the health care system. Although triage is an essential tool to identify symptomatic COVID patients, universal testing strategies should continue simultaneously. Streamlining medical care professionals into self-sufficient teams ensures adequate clinical coverage amongst the suspected COVID, confirmed COVID, and routine labour room admissions.

COVID-19 suspicion and diagnosis in pregnancy: A big conundrum!

Introduction: This article aims to discuss all the challenges faced in the diagnosis of coronavirus disease 2019 (COVID-19) in pregnancy, isolation of suspected and positive patients, their management, and the strategies to prevent the transmission of infection among the healthy population and medical fraternity. The diagnosis of COVID in pregnancy is influenced by many factors, including normal physiological changes in pregnancy, comorbid conditions associated with pregnancy, and the presence of asymptomatic infection in patients. Suspicion of COVID-19 in pregnant females is of utmost importance at a primary health center for risk mitigation of exposure to medical personnel. Material and Methods: A retrospective study was carried out in the labour room in a tertiary care center in India. Two groups were made, suspected COVID and confirmed COVID in pregnant patients. The case records were analysed. Results: Out of a total of 5164 admissions, 95 patients were admitted as suspected (1.8%), but only two patients were COVID-positive amongst them. 84% of COVID-positive patients were asymptomatic. Fever was the most common symptom in both groups (P-value: 0.15). Preeclampsia and anaemia were the most common comorbidities in both groups, not statistically significant. There were 32% of intensive acre unit (ICU) admissions in suspected COVID patients, and 77% of them were having respiratory distress. Conclusion: COVID-19 presents as an asymptomatic infection in most pregnant patients. Physiological changes to the cardiorespiratory and immune systems along with associated comorbidities in pregnancy, increase a woman's susceptibility and delay diagnosis. Consideration of patients as suspected COVID at triage stations on the basis of only contact or travel history poses a great burden on the health care system. Although triage is an essential tool to identify symptomatic COVID patients, universal testing strategies should continue simultaneously. Streamlining medical care professionals into self-sufficient teams ensures adequate clinical coverage amongst the suspected COVID, confirmed COVID, and routine labour room admissions.

High Prevalence of Fungal and NDM-OXA Producing Gram-Negative Bacterial Superinfections in the Second Wave of Coronavirus Disease 2019 in India: Experience from a Dedicated Coronavirus Disease 2019 Hospital in North India.

Introduction: During the second wave of coronavirus disease 2019 (COVID-19), superinfection caused by fungus and multidrug-resistant bacteria worsened the severity of illness in COVID-19 patients. Limited studies from India reported the antimicrobial resistance pattern of secondary infections. In this study, we aim to study the epidemiology of pathogens causing superinfections and genotyping of Gram-negative isolates in COVID-19 patients. Methods: This retrospective study was conducted at a dedicated COVID-19 center, India. The identification of bacteria/fungi was done by Vitek2® and matrix-assisted laser desorption/ionization-time of flight mass spectrometry system. Identification of beta-lactamase genes was done using thermal cycler. The diagnosis of mucormycosis was based on 10% potassium hydroxide direct microscopy. Statistical analyses were performed using STATA version 15.1 (StataCorp., College Station, TX, USA). For continuous variables, mean and standard deviation were computed. For comparing proportions of secondary infections across admission location and outcomes, the Chi-squared test of independence was used. To compare the mean and median between intensive care units and outcomes, an independent t-test and a Mann-Whitney test were used. Results: Of all the clinical samples, 45.4% of samples were cultured positive for secondary infections. Acinetobacter baumannii (35%) was the most common Gram-negative pathogen, while among Gram positive, it was Enterococcus faecium (40%). Among fungus, Candida spp. (61%) predominates followed by molds. Colistin and tigecycline proved effective against these pathogens. blaNDM was the most prevalent gene followed by the blaOX among the carbapenemase genes. Conclusions: The mortality rate among COVID-19 patients with secondary infection was significantly higher compared to the overall mortality rate in COVID-19 patients.

Understanding of COVID-19 vaccination in pregnant female - Hesitancy and acceptance: A prospective observational study

Background: India is one of the most severely affected countries due to the COVID-19 pandemic. A higher risk of severe illness and complications from COVID-19 had been observed in pregnant women as compared to nonpregnant women. The government of India on July 2, 2021, provided approval for the vaccination of pregnant women against COVID-19. A little data regarding the safety or harm during pregnancy of vaccination were available that time. Lack of safety data, fear, mistrust, underestimation of efficacy of vaccine, and chaos due to pandemic makes indecisive surrounding for pregnant women and this causes hesitancy with decision making about the COVID-19 vaccination. Aims and Objectives: This study aims to analyze the willingness and hesitancy of pregnant women to get vaccinated against COVID-19. Materials and Methods: This prospective study was conducted in a tertiary care institute in Northern India. Five hundred antenatal women who were eligible for COVID-19 vaccination were included in this study. Informed consent has been taken and data were analyzed after filling face to face questionnaire regarding vaccine acceptance or hesitancy. Results: The present study revealed low acceptance of COVID-19 vaccination in pregnancy. Prime reasons for the same are no allowance by the family and the possibility of vaccine harming the baby. Conclusion: Specific efforts should be directed toward high-risk populations including pregnant women and those who are planning for pregnancy. This will promote vaccination rates by increasing people's trust in immunization and the health-care system. [ FROM AUTHOR]

Secondary Bacterial Infections in Mucormycosis-COVID-19 Cases: Experience during the Second COVID-19 Wave in India.

In the second wave of COVID-19 in India, there was a new challenge in the form of mucormycosis. Coinfection with mucormycosis was perilous as both conditions required a prolonged hospital stay, thus serving as an ideal platform for secondary infections. Using a retrospective observational study, we studied secondary infections and their impact on the outcome in COVID-19 patients with mucormycosis. The outcome in these patients was evaluated and compared with COVID-19 patients with mucormycosis but without any secondary infection. SPSS V-20 was used for data analysis. Fifty-five patients tested positive for mucormycosis (55/140; 39.28). Twelve out of these 55 (21.8%) developed secondary infections during their hospital stay. Bloodstream infection was the most common (42.86%) secondary infection. The Gram-negative (GN) organisms were more common (11/16; 68.75%) compared with the Gram-positives (GP) (5/16; 31.25%). But the most common isolate was Enterococcus faecium (5/16; 31.25%). A high percentage of microorganisms isolated were multidrug-resistant (15/16; 93.75%). Two out of five (40%) isolates of Enterococcus faecium were vancomycin-resistant (VRE). High resistance to carbapenems was noted in the GN isolates (9/11; 81.81%). The comparison of length of stay in both subgroups was statistically significant (P value <0.001). When compared, the length of stay in people with adverse outcomes was also statistically significant (P value <0.001). Procalcitonin (PCT) had a positive predictive value for the development of secondary bacterial infections (P value <0.001). Antimicrobial stewardship and strict infection control practices are the need of the hour. IMPORTANCE Although our knowledge about COVID-19 and secondary infections in patients is increasing daily, little is known about the secondary infections in COVID-19-mucormycosis patients. Thus, we have intended to share our experience regarding this subgroup. The importance of this study is that it brings to light the type of secondary infections seen in COVID-19-mucormycosis patients. These secondary infections were partially responsible for the mortality and morbidity of the unfortunate ones. We, as health care workers, can learn the lesson and disseminate the knowledge so that in similar situations, health care workers, even in other parts of the world, know what to expect.

Multifunctional Role of S100 Protein Family in the Immune System: An Update.

S100 is a broad subfamily of low-molecular weight calcium-binding proteins (9-14 kDa) with structural similarity and functional discrepancy. It is required for inflammation and cellular homeostasis, and can work extracellularly, intracellularly, or both. S100 members participate in a variety of activities in a healthy cell, including calcium storage and transport (calcium homeostasis). S100 isoforms that have previously been shown to play important roles in the immune system as alarmins (DAMPs), antimicrobial peptides, pro-inflammation stimulators, chemo-attractants, and metal scavengers during an innate immune response. Currently, during the pandemic, it was found that several members of the S100 family are implicated in the pathophysiology of COVID-19. Further, S100 family protein members were proposed to be used as a prognostic marker for COVID-19 infection identification using a nasal swab. In the present review, we compiled the vast majority of recent studies that focused on the multifunctionality of S100 proteins in the complex immune system and its associated activities. Furthermore, we shed light on the numerous molecular approaches and signaling cascades regulated by S100 proteins during immune response. In addition, we discussed the involvement of S100 protein members in abnormal defense systems during the pathogenesis of COVID-19.

Effectiveness of Arsenicum album 30C in Prevention of COVID-19 in Individuals Residing in Containment Zones of Delhi-A Prospective, Community-based, Parallel Cohort Study.

OBJECTIVE: This work was undertaken to evaluate the protective effect of Arsenicum album 30C against COVID-19. DESIGN: The work was designed as a prospective parallel cluster cohort study. INTERVENTION: Participants were enrolled in a homeopathy intervention (HI) cohort (who received Arsenicum album) or in a non-intervention (NI) cohort (who received no systematic intervention) from COVID-19 containment areas of Delhi. Individuals of age 5 years or above were given four medicated pills of Arsenicum album 30C, while those from 1 to 5 years old were given two medicated pills in each dose. RESULTS: The analysis included 10,180 individuals residing in 11 COVID-19 containment areas in Delhi, out of which 6,590 individuals were in the HI cohort and 3,590 individuals were in the NI cohort. The overall protective effect of Arsenicum album 30C was 83.43% (95% confidence interval [CI], 76.77 to 88.17): 45 cases per 6,590 (8.34 per 10,000 person-weeks) in the Arsenicum album 30C group versus 143 cases per 3,590 (45.01 per 10,000 person-weeks) in the NI cohort. The protective effect of Arsenicum album 30C against laboratory confirmed COVID-19 was 74.40% (95% CI, 55.08 to 85.41): 18 cases per 6,590 (3.32 per 10,000 person-weeks) in the Arsenicum album 30C group versus 38 cases per 3,590 (11.85 per 10,000 person-weeks) in the NI cohort. CONCLUSION: The use of Arsenicum album 30C was associated with some protection against probable and laboratory-confirmed COVID-19 in a containment-zone setting. Randomized controlled trials are needed to confirm or refute these results.

Clinical Validation of Standard Q COVID-19 Antigen and IgM/IgG Combo Kit Assay at a Tertiary Care Center in Northern India.

Background Expansion of the testing capacities for severe acute respiratory syndrome-coronavirus-2 is an important issue in the face of ever-increasing case load. So, there is need of point-of-care diagnostic tests in the existing laboratory capacities for early treatment, isolation, and clinical decision making, especially in resource limited settings. Materials and Methods This prospective cohort study was conducted at Jai Prakash Narayan Apex Trauma Center, All India Institute of Medical Sciences, New Delhi. Nasopharyngeal samples and blood samples were collected for antigen and antibody testing. Rapid antigen test was performed as per the kit's instructions. The performance of the kit was compared with the gold standard reverse transcription polymerase chain reaction (RT-PCR) testing. Results Eighty-eight out of 110 patients tested positive by RT-PCR for coronavirus disease 2019 in last 48 to 72 hours were included in the study. Overall, the sensitivity of combined antibody test was 52%, antigen test 26%, and combined sensitivity of both antigen and antibody was 72.7%, respectively. Conclusion The combo kit needs to be used with caution in low prevalence settings, where cases may be missed.

Comparison of Abbott ID NOW, a novel isothermal amplification based COVID-19 diagnostic method with RTPCR.

BACKGROUND: The emergent crisis of the COVID-19 pandemic has posed enormous challenges for clinical laboratories to speed up diagnostics. The current reference standard for the diagnosis of COVID-19 is real time reverse transcriptase PCR on various platforms. However, even with automation, the turnaround time is huge enough to keep up with ever increasing numbers of patients. With increasing surge of COVID cases we need rapid diagnostic tests with good sensitivity and specificity. OBJECTIVES: Comparison between Abbott ID NOW COVID-19 and real time reverse transcriptase PCR as a reference method. MATERIALS AND METHODS: Specimens from seventy-two individuals were obtained over a period of two months which were processed for ID NOW and RTPCR at a dedicated COVID-19 centre of AIIMS. Dry nasal swabs were used for ID NOW while nasopharyngeal swabs along with throat swab were used for RTPCR. Among the participants, 15 were healthcare workers. Mild COVID was seen in 36 participants, moderate in 19 and severe in 9. Eight participants had non COVID illness. RESULTS: From the given samples, we observed that ID NOW has a sensitivity of 93.22% (55/59) specificity 100% (13/13), PPV 100% (55/55) and NPV 76.47% (13/17). CONCLUSION: ID NOW is a convenient, rapid molecular test which makes it suitable for both in laboratory use and as a point of care test. It can be a rapid rule-in test for COVID-19. Negative results, however, have to be interpreted as per the context.

SARS-CoV-2 Rapid Antigen Detection in Respiratory and Nonrespiratory Specimens in COVID-19 Patients.

Rapid antigen testing for coronavirus disease 2019 (COVID-19) available at present provides immediate results at low cost with less expertise and without any need of sophisticated infrastructure. Most of these test kits available are for nasopharyngeal samples. This is a novel study to detect the presence of COVID antigen in samples other than throat and oropharyngeal. Various samples received from patients admitted in the COVID-19 dedicated center were tested for the presence of antigen. Same procedure was followed as done for the nasopharyngeal sample. A total of 150 samples were tested, which included ascitic fluid, pleural fluid, drain fluid, bile, bronchoalveolar lavage, cerebrospinal fluid, endotracheal tube aspirate, sputum, tissue, and urine. Out of 150, 11 (7.33%) were positive and 138 (92.66%) were negative for the antigen test. The COVID-19 antigen test kit, though designed for nasopharyngeal samples, was able to detect the presence of antigen in other clinical samples.

Evaluation of COVID-19 Antigen Fluorescence Immunoassay Test for Rapid Detection of SARS-CoV-2.

INTRODUCTION: Tests detecting SARS-CoV-2-specific antigen have recently been developed, and many of them are now commercially available. However, the real-world performance of these assays is uncertain; therefore, their validation is important. In this study, we have evaluated the performance of STANDARD F COVID-19 antigen fluorescence immunoassay (FIA) kit. METHODS: Nasopharyngeal samples collected from patients were subjected to the test as per manufacturer's instructions. The performance of the kit was compared with the gold standard real-time polymerase chain reaction. RESULTS: A total of 354 patients were tested with STANDARD F COVID-19 antigen FIA test kit. The overall sensitivity, specificity, positive predictive value, and negative predictive value of this test were found to be 38%, 99%, 96.2%, and 72%, respectively, with a diagnostic accuracy of 75.7%. CONCLUSION: STANDARD F COVID-19 antigen FIA showed high specificity and positive predictive value but low sensitivity and negative predictive value.

Immunomodulatory Effects of Vitamin D Supplementation in a Deficient Population.

In addition to its canonical functions, vitamin D has been proposed to be an important mediator of the immune system. Despite ample sunshine, vitamin D deficiency is prevalent (>80%) in the Middle East, resulting in a high rate of supplementation. However, the underlying molecular mechanisms of the specific regimen prescribed and the potential factors affecting an individual's response to vitamin D supplementation are not well characterized. Our objective is to describe the changes in the blood transcriptome and explore the potential mechanisms associated with vitamin D3 supplementation in one hundred vitamin D-deficient women who were given a weekly oral dose (50,000 IU) of vitamin D3 for three months. A high-throughput targeted PCR, composed of 264 genes representing the important blood transcriptomic fingerprints of health and disease states, was performed on pre and post-supplementation blood samples to profile the molecular response to vitamin D3. We identified 54 differentially expressed genes that were strongly modulated by vitamin D3 supplementation. Network analyses showed significant changes in the immune-related pathways such as TLR4/CD14 and IFN receptors, and catabolic processes related to NF-kB, which were subsequently confirmed by gene ontology enrichment analyses. We proposed a model for vitamin D3 response based on the expression changes of molecules involved in the receptor-mediated intra-cellular signaling pathways and the ensuing predicted effects on cytokine production. Overall, vitamin D3 has a strong effect on the immune system, G-coupled protein receptor signaling, and the ubiquitin system. We highlighted the major molecular changes and biological processes induced by vitamin D3, which will help to further investigate the effectiveness of vitamin D3 supplementation among individuals in the Middle East as well as other regions.

Profile of co-infections & secondary infections in COVID-19 patients at a dedicated COVID-19 facility of a tertiary care Indian hospital: Implication on antimicrobial resistance.

BACKGROUND: The COVID-19 pandemic has raised concerns over secondary infections because it has limited treatment options and empiric antimicrobial treatment poses serious risks of aggravating antimicrobial resistance (AMR). Studies have shown that COVID-19 patients are predisposed to develop secondary infections. This study was conducted to ascertain the prevalence and profiles of co- & secondary infections in patients at the COVID-19 facility in North India. METHODS: We studied the profile of pathogens isolated from 290 clinical samples. Bacterial and fungal pathogens were identified, and antimicrobial susceptibility was determined by the Vitek2® system. Additionally, respiratory samples were tested for any viral/atypical bacterial co-infections and the presence of AMR genes by FilmArray test. The clinical and outcome data of these patients were also recorded for demographic and outcome measures analyses. RESULTS: A total of 151 (13%) patients had secondary infections, and most got infected within the first 14 days of hospital admission. Patients aged >50 years developed severe symptoms (p = 0.0004) and/or had a fatal outcome (p = 0.0005). In-hospital mortality was 33%.K.pneumoniae (33.3%) was the predominant pathogen, followed by A. baumannii (27.1%). The overall resistance was up to 84%.Majority of the organisms were multidrug-resistant (MDR) harbouring MDR genes. CONCLUSION: A high rate of secondary infections with resistant pathogens in COVID-19 patients highlights the importance of antimicrobial stewardship programs focussing on supporting the optimal selection of empiric treatment and rapid-de-escalation, based on culture reports.

Promising role of defensins peptides as therapeutics to combat against viral infection.

Antimicrobial peptides (AMPs) are ubiquitously present small peptides, which play a critical function in the innate immune system. The defensin class of AMPs represented an evolutionarily ancient family containing cationic cysteine residue and frequently expressed in epithelial or neutrophils cells. It plays myriad functions in host innate immune responses against various infection. Defensin has a broad spectrum of antimicrobial activities, including anti-bacteria, anti-viruses (AVPs), anti-fungi, anti-cancers, and also overcoming bacterial drug resistance. In this review, we compiled the progress on defensin, particularly incorporating the mechanism of action, their application as an antiviral agent, prospects in different areas, and limitations to be solved as an antiviral peptide. Defensins were explored, in particular, their capacity to stimulate innate and adaptive immunity by trigging as anti-coronavirus (COVID-19) peptides. The present review summarised its immunomodulatory and immunoenhancing properties and predominantly focused on its promising therapeutic adjuvant choices for combat against viral infection.

Rapid chromatographic immunoassay-based evaluation of COVID-19: A cross-sectional, diagnostic test accuracy study & its implications for COVID-19 management in India.

Background & objectives: Coronavirus disease 2019 (COVID-19) has so far affected over 41 million people globally. The limited supply of real-time reverse transcription-polymerase chain reaction (rRT-PCR) kits and reagents has made meeting the rising demand for increased testing incompetent, worldwide. A highly sensitive and specific antigen-based rapid diagnostic test (RDT) is the need of the hour. The objective of this study was to evaluate the performance of a rapid chromatographic immunoassay-based test (index test) compared with a clinical reference standard (rRT-PCR). Methods: A cross-sectional, single-blinded study was conducted at a tertiary care teaching hospital in north India. Paired samples were taken for RDT and rRT-PCR (reference standard) from consecutive participants screened for COVID-19 to calculate the sensitivity and specificity of the RDT. Further subgroup analysis was done based on the duration of illness and cycle threshold values. Cohen's kappa coefficient was used to measure the level of agreement between the two tests. Results: Of the 330 participants, 77 were rRT-PCR positive for SARS-CoV-2. Sixty four of these patients also tested positive for SARS-CoV-2 by RDT. The overall sensitivity and specificity were 81.8 and 99.6 per cent, respectively. The sensitivity of RDT was higher (85.9%) in participants with a duration of illness ≤5 days. Interpretation & conclusions: With an excellent specificity and moderate sensitivity, this RDT may be used to rule in COVID-19 in patients with a duration of illness ≤5 days. Large-scale testing based on this RDT across the country would result in quick detection, isolation and treatment of COVID-19 patients.