Reflection of Epidemiological Impact on Burden of Injury in Tertiary Care Centre, Pre-COVID and COVID Era: "Lockdown, a Good Fortune for Saving Life and Limb".

Road traffic injuries continue to be a major public health concern and are a leading cause of death and injury across the world. Road transport remains the most favoured mode of transport for both freight and passenger movement in India. As per the World Health Organization, approximately 1.35 million people die annually on the world's roads, and another 20 to 50 million sustain nonfatal injuries as a result of road traffic crashes. These injuries and deaths have an immeasurable impact on the families affected, whose lives are often changed irrevocably by these tragedies, and on the communities in which these people lived and worked. India ranks 1 in the total number of traffic-related deaths across the 199 countries reported in the World Road Statistics, 2018, followed by China and the USA due to its large population (India, 21.7, and China, 18.6, fatalities per 100,000), although several Central American and African countries have higher fatality rates. During COVID-19 (coronavirus disease-19) pandemic, a national lockdown was implemented by Government of India from 24 March to 31 May 2020, in four phases to control the spread of SARS CoV-2 (severe acute respiratory syndrome coronavirus-2) infection. In our observational study, we compared the epidemiology of trauma patients of two periods from 1 April to 31 May 2019 and 24 March to 31 May 2020 and found out that unique concept of lockdown with stringent implementation of discipline, alcohol ban, behavioural change in visiting family and friends as minimum as possible, promoting work from home and digital classes for school and colleges lead to phenomenal decrease in traffic-related injuries and fatality. The lockdown has grossly decreased 'disability-adjusted life year'(DALY), an outcome indicator for cost-effective analysis, which is calculated as the value of future years of healthy life lost to morbidity/disability and future years of life lost to premature mortality.

Determinants of stroke in patients with rhino cerebral mucormycosis seen during the second wave of COVID-19 pandemic: A prospective cohort study.

BACKGROUND: Rhino cerebral mucormycosis is an uncommon opportunistic infection of the nasal sinuses and brain, and a group of saprophytic fungi causes it. During the second wave of COVID-19, India witnessed an unprecedented number of patients with rhino cerebral mucormycosis. Invasion of the cavernous sinus and occlusion of the internal carotid artery in many cases resulted in a stroke. The study aimed to assess the clinical and neuroimaging predictors of stroke in patients with rhino cerebral mucormycosis. We also evaluated the predictors of death in these patients at 90 days. METHODS: A prospective study was performed at a tertiary care centre in India between July 2021 and September 2021. We enrolled consecutive microbiologically confirmed patients of rhino cerebral mucormycosis. All patients underwent neuroimaging of the brain. Treatment comprised of anti-fungal drugs and endoscopic nasal/sinus debridement. We followed the patients for 90 days and assessed the predictors of stroke and mortality RESULTS: Forty-four patients with rhino cerebral mucormycosis were enrolled. At inclusion, in 24 patients, the RT-PCR test for SARS-COV-2 was negative. Diabetes mellitus was the most frequent (72.7 %) underlying risk factor; in most, diabetes mellitus was recently discovered. At inclusion or subsequent follow-up, stroke was seen in 11 (25 %) patients. Only seven patients had hemiparesis. Imaging revealed internal carotid artery occlusion in 17 (38.6 %) patients. Hypertension, corticosteroid use, and cavernous sinus thrombosis were independent predictors of stroke. Nine (20.5 %) died during follow-up, and stroke was an independent predictor of death. CONCLUSION: Stroke indicated poor prognosis among rhino cerebral mucormycosis patients encountered during the second wave of the COVID-19 epidemic.

Tracing the origin of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): A systematic review and narrative synthesis.

The aim of the study was to trace and understand the origin of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through various available literatures and accessible databases. Although the world enters the third year of the coronavirus disease 2019 pandemic, health and socioeconomic impacts continue to mount, the origin and mechanisms of spill-over of the SARS-CoV-2 into humans remain elusive. Therefore, a systematic review of the literature was performed that showcased the integrated information obtained through manual searches, digital databases (PubMed, CINAHL, and MEDLINE) searches, and searches from legitimate publications (1966-2022), followed by meta-analysis. Our systematic analysis data proposed three postulated hypotheses concerning the origin of the SARS-CoV-2, which include zoonotic origin (Z), laboratory origin (L), and obscure origin (O). Despite the fact that the zoonotic origin for SARS-CoV-2 has not been conclusively identified to date, our data suggest a zoonotic origin, in contrast to some alternative concepts, including the probability of a laboratory incident or leak. Our data exhibit that zoonotic origin (Z) has higher evidence-based support as compared to laboratory origin (L). Importantly, based on all the studies included, we generated the forest plot with 95% confidence intervals (CIs) of the risk ratio estimates. Our meta-analysis further supports the zoonotic origin of SARS/SARS-CoV-2 in the included studies.

Seropositivity of Anti-SARS CoV2 IgG antibodies in health care workers of an Indian tertiary care hospital during COVID-19.

PURPOSE: Health care workers [HCW] are at a higher risk of infection SARS CoV2 infection due to frequent and close contact to patients with COVID-19. METHODS: Serum samples from 500 HCW's were tested for SARS CoV2 IgG antibodies in October 2020. A questionnaire was used to collect demographic and clinical data. All these HCWs were tested for COVID-19, in 2nd week of September 2020, as a hospital policy. RESULTS: Anti SARS CoV2 antibodies were detected in 128/ 500 [25.6%] HCWs. A total of 195/ 500 [39%] enrolled cases had already tested positive for Covid-19 at least once in last six months by RT-PCR. Sixty eight percent of HCWs with previous COVID-19 positivity by RT- PCR tested positive for Anti SARS CoV2 antibodies, whereas only 2.76% of asymptomatic HCWs tested positive. Of 121 anti SARS-CoV-2 IgG positive persons, 70 [57.85%] had CT value â€‹< â€‹25. Low CT value and asymptomatic cases had a strong reverse statistically significant association with SARS CoV2 IgG antibody positivity. CONCLUSIONS: We report that sero-conversion rate in HCWs is similar to that in general population suggesting that preventive practices used in hospitals are satisfactory. Cases with low viral counts in respiratory sample and asymptomatic cases have lower rate of seroconversion.

Understanding the Prevalence and Geographic Heterogeneity of SARS-CoV-2 Infection: Findings of the First Serosurvey in Uttar Pradesh, India.

Population-based serological antibody test for SARS-CoV-2 infection helps in estimating the exposure in the community. We present the findings of the first district representative seroepidemiological survey conducted between 4 and 10 September 2020 among the population aged 5 years and above in the state of Uttar Pradesh, India. Multi-stage cluster sampling was used to select participants from 495 primary sampling units (villages in rural areas and wards in urban areas) across 11 selected districts to provide district-level seroprevalence disaggregated by place of residence (rural/urban), age (5-17 years/aged 18 +) and gender. A venous blood sample was collected to determine seroprevalence. Of 16,012 individuals enrolled in the study, 22.2% [95% CI 21.5-22.9] equating to about 10.4 million population in 11 districts were already exposed to SARS-CoV-2 infection by mid-September 2020. The overall seroprevalence was significantly higher in urban areas (30.6%, 95% CI 29.4-31.7) compared to rural areas (14.7%, 95% CI 13.9-15.6), and among aged 18 + years (23.2%, 95% CI 22.4-24.0) compared to aged 5-17 years (18.4%, 95% CI 17.0-19.9). No differences were observed by gender. Individuals exposed to a COVID confirmed case or residing in a COVID containment zone had higher seroprevalence (34.5% and 26.0%, respectively). There was also a wide variation (10.7-33.0%) in seropositivity across 11 districts indicating that population exposed to COVID was not uniform at the time of the study. Since about 78% of the population (36.5 million) in these districts were still susceptible to infection, public health measures remain essential to reduce further spread.

COVID-19-associated Guillain-Barre syndrome: Postinfectious alone or neuroinvasive too?

Coronavirus disease 2019 (COVID-19) has been shown to be associated with a lot of neurological complications, of whom Guillain-Barre syndrome (GBS) is an important post-infectious consequentiality. More than 220 patients with GBS have been reported thus far. We intend to share our experience with five patients of GBS where one of them had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the cerebrospinal fluid (CSF). This is the first-ever report demonstrating the presence of SARS-CoV-2 in the CSF of an adult patient; a similar occurrence has recently been described in a pediatric patient. We wish to emphasize the fact that commonly GBS occurs as a result of a post-infectious process but in a few cases where the symptoms of COVID-19 and GBS occur concurrently, corresponding to the viremic phase, separate pathogenesis needs to be thought of. This para-infectious nature is exemplified by the presence of virus in the cerebrospinal fluid of one of our patients. We review the neuroinvasive potential of SARS-Cov-2 in this regard and draw parallels with Cytomegalovirus, Zika virus, and Human Immunodeficiency virus-associated occurrences of GBS.

An Epidemiological Analysis of SARS-CoV-2 Genomic Sequences from Different Regions of India.

The number of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) cases is increasing in India. This study looks upon the geographic distribution of the virus clades and variants circulating in different parts of India between January and August 2020. The NPS/OPS from representative positive cases from different states and union territories in India were collected every month through the VRDLs in the country and analyzed using next-generation sequencing. Epidemiological analysis of the 689 SARS-CoV-2 clinical samples revealed GH and GR to be the predominant clades circulating in different states in India. The northern part of India largely reported the 'GH' clade, whereas the southern part reported the 'GR', with a few exceptions. These sequences also revealed the presence of single independent mutations-E484Q and N440K-from Maharashtra (first observed in March 2020) and Southern Indian States (first observed in May 2020), respectively. Furthermore, this study indicates that the SARS-CoV-2 variant (VOC, VUI, variant of high consequence and double mutant) was not observed during the early phase of virus transmission (January-August). This increased number of variations observed within a short timeframe across the globe suggests virus evolution, which can be a step towards enhanced host adaptation.

Feasibility, efficiency & effectiveness of pooled sample testing strategy (pooled NAAT) for molecular testing of COVID-19.

BACKGROUND & OBJECTIVES: During the current COVID-19 pandemic, a large number of clinical samples were tested by real-time PCR. Pooling the clinical samples before testing can be a good cost-saving and rapid alternative for screening large populations. The aim of this study was to compare the performance characteristics, feasibility and effectiveness of pooling nasal swab and throat swab samples for screening and diagnosis of SARS-CoV-2. METHODS: The pool testing was applied on a set of samples coming from low COVID-19 positivity areas. A total of 2410 samples were tested in pools of five samples each. A total of five pools of five samples each were generated and tested for E gene. RESULTS: Of the total of 482 pools (2410 samples) 24 pools flagged positive. Later on pool de-convolution, a total of 26 samples were detected as positive for COVID-19, leading to positivity of about one per cent in the test population. For the diagnosis of individual samples, the pooling strategies resulted in cost savings of 75 per cent (5 samples per pool). INTERPRETATION & CONCLUSIONS: It was observed that testing samples for COVID-19 by reverse transcription (RT)- PCR after pooling could be a cost-effective method which would save both in manpower and cost especially for resource-poor countries and at a time when test kits were short in supply.

SARS-CoV-2 -RNA persists longer in faecal sample as compared to nasal and throat swab samples of COVID-19 patients'; an observational study.

The route of transmission of Novel SARS-CoV-2 virus is ambiguous. In this regard we planned a study to find out SARS-CoV-RNA shedding in various clinical samples of 9 COVID-19 positive patients. SARS-CoV-RNA was detected in nasal swab (NS), throat swab (TS) and faecal sample but was not detected in serum and urine samples. We also report that SARS-CoV-2-RNA persisted in faeces for >20 days. Persistence of faecal RNA might impose challenge in infection control and the disease may spread to household contacts if discharged. Perineal cleaning and hygiene may be advised at the time of vaginal delivery.

Pooled testing for COVID-19 diagnosis by real-time RT-PCR: A multi-site comparative evaluation of 5- & 10-sample pooling.

BACKGROUND & OBJECTIVES: Public health and diagnostic laboratories are facing huge sample loads for COVID-19 diagnosis by real-time reverse transcription-polymerase chain reaction (RT-PCR). High sensitivity of optimized real-time RT-PCR assays makes pooled testing a potentially efficient strategy for resource utilization when positivity rates for particular regions or groups of individuals are low. We report here a comparative analysis of pooled testing for 5- and 10-sample pools by real-time RT-PCR across 10 COVID-19 testing laboratories in India. METHODS: Ten virus research and diagnostic laboratories (VRDLs) testing for COVID-19 by real-time RT-PCR participated in this evaluation. At each laboratory, 100 nasopharyngeal swab samples including 10 positive samples were used to create 5- and 10-sample pools with one positive sample in each pool. RNA extraction and real-time RT-PCR for SARS-CoV-2-specific E gene target were performed for individual positive samples as well as pooled samples. Concordance between individual sample testing and testing in the 5- or 10-sample pools was calculated, and the variation across sites and by sample cycle threshold (Ct) values was analyzed. RESULTS: A total of 110 each of 5- and 10-sample pools were evaluated. Concordance between the 5-sample pool and individual sample testing was 100 per cent in the Ct value ≤30 cycles and 95.5 per cent for Ctvalues ≤33 cycles. Overall concordance between the 5-sample pooled and individual sample testing was 88 per cent while that between 10-sample pool and individual sample testing was 66 per cent. Although the concordance rates for both the 5- and 10-sample pooled testing varied across laboratories, yet for samples with Ct values ≤33 cycles, the concordance was ≥90 per cent across all laboratories for the 5-sample pools. INTERPRETATION & CONCLUSIONS: Results from this multi-site assessment suggest that pooling five samples for SARS-CoV-2 detection by real-time RT-PCR may be an acceptable strategy without much loss of sensitivity even for low viral loads, while with 10-sample pools, there may be considerably higher numbers of false negatives. However, testing laboratories should perform validations with the specific RNA extraction and RT-PCR kits in use at their centres before initiating pooled testing.

COVID-19: An up-to-date review - from morphology to pathogenesis.

The entire world is under a devastating pandemic caused by COVID-19 with a high mortality rate. Knowledge of the viral structure, factors that help in its progression and spread, pathological findings, diagnostic methods and, treatment modalities helps in understanding the viral disease and also in treating the patients in a better way besides preventing the community spread of this deadly infection. The causative agent is a single- stranded RNA virus. The clinical spectrum varies in symptomatic and asymptomatic patients, who later become potential silent carriers, thus unknowingly spreading the virus. The virus constantly undergoes recombination, with reports of cross-species infections. Studies have indicated a strong immunological basis of COVID-19 infection. Not only does it weaken the immune system causing multi-organ involvement but also helps in its progression and spread to others.Multiple organs especially lungs, heart, kidney, gastrointestinal and hepatic system, brain and skin are affected varying in their severity. Similarly, persons with associated co-morbidities are likely to be affected more in terms of the number as well as in the severity. Real- time reverse transcription polymerase chain reaction confirms the presence of COVID-19 infection. Serological diagnosis helps in diagnosing an ongoing outbreak or retrospective infection. Furthermore, it also identifies individuals who have been infected or have recovered from the disease especially the asymptomatic. This helps in the development of an effective vaccine indicating the status of herd immunity in the community. Different treatment modalities are being tried and under trial. This review article thus highlights the global epidemiological status, characteristic of the virus, symptomatology of the patients, role of diagnostic tests available, organs affected including their morphological changes and the latest line of treatment of COVID-19.

Laboratory preparedness for SARS-CoV-2 testing in India: Harnessing a network of Virus Research & Diagnostic Laboratories.

Background & objectives: An outbreak of respiratory illness of unknown aetiology was reported from Hubei province of Wuhan, People's Republic of China, in December 2019. The outbreak was attributed to a novel coronavirus (CoV), named as severe acute respiratory syndrome (SARS)-CoV-2 and the disease as COVID-19. Within one month, cases were reported from 25 countries. In view of the novel viral strain with reported high morbidity, establishing early countrywide diagnosis to detect imported cases became critical. Here we describe the role of a countrywide network of VRDLs in early diagnosis of COVID-19. Methods: The Indian Council of Medical Research (ICMR)-National Institute of Virology (NIV), Pune, established screening as well as confirmatory assays for SARS-CoV-2. A total of 13 VRDLs were provided with the E gene screening real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay. VRDLs were selected on the basis of their presence near an international airport/seaport and their past performance. The case definition for testing included all individuals with travel history to Wuhan and symptomatic individuals with travel history to other parts of China. This was later expanded to include symptomatic individuals returning from Singapore, Japan, Hong Kong, Thailand and South Korea. Results: Within a week of standardization of the test at NIV, all VRDLs could initiate testing for SARS-CoV-2. Till February 29, 2020, a total of 2,913 samples were tested. This included both 654 individuals quarantined in the two camps and others fitting within the case definition. The quarantined individuals were tested twice - at days 0 and 14. All tested negative on both occasions. Only three individuals belonging to different districts in Kerala were found to be positive. Interpretation & conclusions: Sudden emergence of SARS-CoV-2 and its potential to cause a pandemic posed an unsurmountable challenge to the public health system of India. However, concerted efforts of various arms of the Government of India resulted in a well-coordinated action at each level. India has successfully demonstrated its ability to establish quick diagnosis of SARS-CoV-2 at NIV, Pune, and the testing VRDLs.