GENOMIC PROFILING OF SARS-COV-2 STRAINS CIRCULATING IN SOUTH EASTERN REGION OF INDIA DURING THREE WAVES OF PANDEMIC (preprint)

Continuous bio-surveillance of SARS-CoV-2 is an ongoing task at local, national and global levels since the pandemic onset for understanding genetic evolution and vaccine efficacy. Present study was designed to track the emergence of new variants along the duration of three peaks of infection in the city of Puducherry, India. A total of 128 samples were subjected to Illumina deep RNA sequencing. The results showed predominance of uncommon, delta and omicron variants in first, second and third waves respectively. The most common pangolin lineage was B.1.560 and B.1.617.2. The study observed a total of 3133 common and 11 new mutations. The most common is in the Spike_D614G. A new set of mutations was observed in key viral factors such as NS16 that are implicated to be involved in immune evasion. This may have impact on enhanced disease virulence, vaccine efficiency and possible tolerance to current antivirals. This warrants further in vitro studies to understand the significance of the mutations. While the results presented would also augment the ongoing research on evolutionary and the genetic epidemiology of SARS-CoV-2, it also emphasizes the need for continuous genetic monitoring to predict the forthcoming threats due to the emergence of new or existing variants.

Restoration of vascular endothelial integrity by mesenchymal stromal/stem cells in debilitating virus diseases.

Endothelial dysfunction is one of the key cornerstone complications of emerging and re-emerging viruses which lead to vascular leakage and a high mortality rate. The mechanism that regulates the origin of endothelial dysregulation is not completely elucidated. Currently, there are no potential pharmacological treatments and curable management for such diseases. In this sense, mesenchymal stromal/stem cells (MSCs) has been emerging to be a promising therapeutic strategy in restoring endothelial barrier function in various lung disease, including ALI and ARDS. The mechanism of the role of MSCs in restoring endothelial integrity among single-strand RNA (ssRNA) viruses that target endothelial cells remains elusive. Thus, we have discussed the therapeutic role of MSCs in restoring vascular integrity by (i) inhibiting the metalloprotease activity thereby preventing the cleavage of tight junction proteins, which are essential for maintaining membrane integrity (ii) possessing antioxidant properties which neutralize the excessive ROS production due to virus infection and its associated hyper host immune response (iii) modulating micro RNAs that regulate the endothelial activation and its integrity by downregulating the inflammatory response during ssRNA infection.

Study on the incidence of nosocomialinfections in COVID19 patients inatertiary care Hospital

Aim:ToknowtheincidenceofnosocomialinfectionsintheCOVID19patientsadmitted in the hospital that may help in the selection of the suitable antibiotics followsthebetter managementof theCOVID 19patients.Materials and methods: A total of 1534 COVID 19 patients were includedin thestudy.Therespiratory,blood,urinaryandpusformsurgicalsitessampleswerecollected to find the incidence of the bacterial infection in hospitalized COVID 19patients. The samples were collected 48 hours after the admission of the patient in to thehospital.Results: The incidence of the nosocomial infections in the COVID 19 patients was30.24%. The Staphylococcus aureus, Klebsiellapneumoniae, and Coagulase negativestaphylococci were more prevalent bacteria causing secondary infection in COVID 19patients.E.coliwas predominantly seeninUrinesamples.Conclusion: The rate of bacterial infections in the COVID 19 patients was observed ashighandneedtobeconsideredtotakeprecautionstominimisethespreadofnosocomial infections. The incidence of the bacteria reported in this study may be ofgreat value in the management of the COVID 19 patients and may also help to reducethemortality and morbidity.

Early shedding of membrane-bounded ACE2 could be an indicator for disease severity in SARS-CoV-2.

SARS-CoV-2 uses membrane bound Angiotensin-Converting Enzyme 2 (ACE2) as a key host receptor for its entry. However, inconsistent results are available in terms of shedding of membrane ACE2 and circulating levels of soluble ACE2 during SARS-CoV-2. To ascertain soluble ACE2 as an effective biomarker for the prediction of COVID-19 outcome, in the present study, we investigated the levels of plasma ACE2 during the early phase of infection in COVID-19 patients. The study involved a total of 42 COVID-19 patients along with 10 healthy controls. Plasma levels of ACE2 was determined using ELISA at the time of admission and on day 7 post admission. The association of sACE2 with D-dimer a marker for hyper-coagulation was performed using a dependence test. Compared to healthy controls, SARS-CoV-2 cases has shown a huge increase in the sACE2 at the time of admission. During the course of infection, we found a significant increase (P ≤ 0.001) in sACE2 in severe cases compared to moderate. There was a strong increase in sACE2 in cases with hypertension and diabetes mellitus. Interestingly, a strong positive correlation (P ≤ 0.001) was obtained between sACE2 and D-dimer. Thus, an excessive shedding of ACE2 during the early phase is a common phenomenon in severe form of the SARS-CoV-2. Along with D-dimer, the sACE2 levels could serve as a clinical biomarker for the prediction of disease outcome. However further studies are needed to ascertain its role in host-virus interplay.

Comparison of Characteristics of US International Travelers Seeking Pretravel Health Consultations at US Global TravEpiNet Sites before and during the COVID-19 Pandemic

Background. In January-March 2020, the Centers for Disease Control and Prevention (CDC) issued multiple warnings regarding COVID-19 travel-associated risks. We sought to describe US travelers seeking pretravel consultation regarding international travel at US Global TravEpiNet (GTEN) sites before and after the initial COVID-19 travel warnings. Methods. We prospectively collected data at 22 GTEN sites pre-COVID-19 (January-December 2019) and 18 GTEN sites during the COVID-19 pandemic (April 2020-March 2021). We excluded travelers evaluated during January-March 2020, when CDC travel guidance was evolving rapidly. Travelers used standardized questionnaires to self-report data regarding demographics and travel-related characteristics. Providers confirmed these data and documented their recommendations during pretravel consultation, which could be performed virtually. We conducted descriptive analyses of differences in demographics, travel-related characteristics, vaccinations, and medications (SAS v9.4;Cary, NC). Results. Compared with 16,903 pre-COVID-19 consultations, only 1,564 consultations occurred during the COVID-19 pandemic, a 90% reduction (Table). During COVID-19, a greater proportion of travelers were children aged 1-5 years, visiting friends and relatives (VFR), with itineraries ≥ 30 days, and going to Africa;a smaller proportion of travelers were aged > 55 years, or traveling to Southeast Asia or the Western Pacific. During COVID-19, fewer vaccine-eligible travelers received vaccines at the pretravel consultation except for yellow fever, and a greater proportion were referred to another provider for vaccination (Figure). Table. Demographics and travel-related characteristics of international travelers seeking pretravel consultation at Global TravEpiNet sites before and during the COVID-19 pandemic Table continued. Demographics and travel-related characteristics of international travelers seeking pretravel consultation at Global TravEpiNet sites before and during the COVID-19 pandemic Figure. Vaccinations and reasons for nonvaccination among vaccine-eligible international travelers at pretravel consultations at Global TravEpiNet (GTEN) sites before and during the COVID-19 pandemic. Among vaccine-eligible travelers, we summarized those who were vaccinated at the visit (blue) and not vaccinated (orange). We then categorized reasons for nonvaccination into: provider decision (solid), referral to another provider (dots), traveler refusal (striped), or other (hatched). COVID-19 vaccination was not available at GTEN sites during the analysis period;although COVID-19 vaccinations outside of GTEN sites might have affected vaccination recommendations, they were unlikely to have had a large effect given their limited availability in January-March 2021. Conclusion. Compared with pre-COVID-19, US travelers seeking pretravel consultations at GTEN sites during the pandemic might be at higher risk for travel-related infections given VFR status, traveling for ≥ 30 days, and going to Africa. Fewer vaccine-eligible travelers were vaccinated at pretravel consultations, which could reflect more virtual pretravel consultations. Counseling and vaccination for international travelers continue to be priorities during the COVID-19 pandemic.

COVID-19 palliative and end of life care plan (COPE-CP): Development and audit of outcomes

Background and aim: Palliative care (PC) referral in serious COVID-19 patients improves decision-making, optimal health resource utilization, end-of-life symptom management, and family support. Development of a systematic decision-making matrix for PC referral for serious COVID-19 patients and an audit of its outcomes were explored in this study. Methods: Phase 1: A decision-making matrix for PC referral along with algorithms for managing symptoms and psychosocial needs of serious COVID-19 patients and their families were developed. Phase 2: Audit of outcomes of PC referral in hospitalized serious COVID- 19 patients was conducted using a pre-designed proforma. Disease demographics, illness variables, symptom management needs, and endof- life care preferences were recorded and analyzed. Results: Out of 1575 COVID-19 inpatients, 50 (3.1%) were referred to palliative care. Among 190 COVID-19 related hospital deaths, 20% (38) received end-of-life care. 88% were referred from ICUs, with 84% having >2 comorbid conditions. The median length of hospital stay was 14 days;the median duration between PC referral and death was 4 days. Among those who died with serious COVID-19 illness, PC referral had no impact on the duration of hospital and ICU stay. Among the 50 referred for PC, 47 (94%) were referred for goals of care discussion. 78% received opioids, 70% benzodiazepines, and 42% haloperidol for symptom management. 48 (96%) families participated in PC family meetings for documentation of end-of-life care preferences and 31 (62%) opted for limitation of life-sustaining treatment. 31 (62%) patients died in the ICU, while 7 (14%) died in the palliative medicine high-dependency unit. Psychosocial and bereavement support was offered to all. Conclusion: COPE-CP was accepted and implemented in the COVID ICU. PC referral enabled access to management of end-of-life symptoms and facilitated limitation of life-sustaining treatment in serious COVID-19 patients.

COVID-19 Pandemic-Frontline Experiences and Lessons Learned From a Tertiary Care Teaching Hospital at a Suburban Location of Southeastern India.

The key challenges to any health care setup during emergency situations, such as that of the COVID-19 pandemic would be to rapidly address hospital preparedness and response tailored to the local population, societal influences, political factors within the existing infrastructure, and workforce. Second, to adopt and moderate policies, standard operating procedures (SOPs) and guidelines issued by national and international agencies, such as WHO, CDC, and the Indian Council for Medical Research (ICMR) were tailor-made to the local conditions of the hospital and community. In this publication, we have discussed the challenges and experiences in preparation and responses to the ongoing COVID-19 pandemic at a tertiary teaching hospital situated at a suburban locale in a small union territory. Puducherry is located in the South Eastern Coromandel Coast of India. The core processes, such as hospital preparedness, adoption, and amendments to SOPs based on dynamic changes in guidelines released by the central and local government, training given to health care workers, setting up the in-house diagnostic facility, surge capacity, management of supplies during the lockdown, infection prevention, and control and patient care are discussed. We have also reinforced our experiences in translating COVID-related opportunities for research and innovation in the form of awards and research proposals for the faculty and students of our institute. The lessons learned in terms of strength and limitations on the ground level of public health during this process is worth sharing as it would provide guidance in preparing the health care setups for pre- and post-pandemic.

Potential biomarkers for the early prediction of SARS-COV-2 disease outcome.

The current pandemic due to the fast spreading of SARS-CoV-2 infection has caused severe impairment in health, social, economic, scientific, and medical sectors across the globe. Owing to the not so well understood mechanism of disease pathogenesis in terms of variations in immune responses, there remains obscure why some of the patients who are infected by the novel SARS-CoV-2 develop an unpredictable clinical course that rapidly causes severe and deadly complications/manifestations. Currently, several assays are available for the confirmation of SARS-CoV-2 infection at the point of care. However, none of these assays can predict the severity of the COVID-19 disease. Thus, the identification of a prognostic biomarker that forecasts the condition of SARS-CoV-2 patients to develop a severe form of the disease could enable the clinicians for more efficient patient triage and treatment. In this regard, the present review describes the role of selected biomolecules that are crucially involved in the immune-pathogenesis of SARS-CoV-2 infection such as hyper-immune responsiveness, bradykinin storm and vascular leakage assuming these may serve as an effective prognostic biomarker in COVID-19 to understand the outcome of the disease. Based on the review, we also propose the development of a cost-effective SERS-based prognostic biosensor for the detection and quantification of biomolecules for use as a point-of-care system during a disease outbreak.