Delta Variant SARS-CoV-2 infections in pediatric cases during the second wave in India (preprint)

The aim of this study was to identify the SARS-CoV-2 lineages circulating in the pediatric population of India during the second wave of the pandemic. Clinical and demographic details linked with the nasopharyngeal/oropharyngeal swabs (NPS/OPS) collected from SARS-CoV-2 cases (n=583) aged 0-18 year and tested positive by real-time RT-PCR were retrieved from March to June 2021.Symptoms were reported among 37.2% of patients and 14.8% reported to be hospitalized. The E gene CT value had significant statistical difference at the point of sample collection when compared to that observed in the sequencing laboratory. Out of these 512 sequences 372 were VOCs, 51 were VOIs. Most common lineages observed were Delta, followed by Kappa, Alpha and B.1.36, seen in 65.82%, 9.96%, 6.83% and 4.68%, respectively in the study population. Overall, it was observed that Delta strain was the leading cause of SARS-CoV-2 infection in Indian children during the second wave of the pandemic. We emphasize on the need of continuous genomic surveillance in SARS-CoV-2 infection even amongst children.

Assessment of Post COVID-19 Health Problems and its Determinants in North India: A descriptive cross section study (preprint)

With millions of people getting affected with COVID-19 pandemic caused by a novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), people living with post COVID-19 Symptoms (PCS) are expected to rise in the future{middle dot} The present study aimed at assessing PCS comprehensively and its associated factors among COVID-19 recovered adult population in north India. MethodsIn a tertiary health centre at Delhi, an online based cross-sectional study was conducted using a semi-structured questionnaire, developed by employing a nominal group technique, in aged 18 years and above who were SARS-CoV-2 positive during the month of January to April 2021. Socio-demographic, various potential risk factors, including pre-existing morbidities, vaccination status, and severity of acute COVID-19 illness, information on acute illness for management and a spectrum of PCS were collected between June 16 to July 28, 2021. Each participant was contacted telephonically before sending the survey link. PCS were presented as relative frequency; chi-square test, odds ratio, including adjusted, were calculated to rule out association between PCS and potential predictors. ResultsA total of 773 of 1801 COVID recovered participants responded to the link reaching a participation rate of 42{middle dot}9%, with a median age of 34 years (IQR 27 to 44). Male respondents were 56{middle dot}4%. Around 33{middle dot}2% of them had PCS at four or more weeks, affecting almost all body organ systems. The most prevalent PCS were fatigue (79{middle dot}3%), pain in the joins (33{middle dot}4%), muscle (29{middle dot}9%), hair loss (28{middle dot}0%), headache (27{middle dot}2%), breathlessness (25{middle dot}3%), sleep disturbance (25{middle dot}3%) and cough (24{middle dot}9%). The prevalence of PCS was reduced to 12{middle dot}8% at 12 weeks after positive test. Factor such as female gender, older age, oxygen supplementation during the acute illness, working in healthcare care facilities, the severity of acute illness, and pre-existing co-morbid were risk factors for PCS. Further, vaccination (second dose) reduced the odds of developing PCS by 45% compared to unvaccinated participants (aOR 0{middle dot}65; 95%CI 0{middle dot}45-0{middle dot}96). Finally, 8{middle dot}3% of participants rated their overall health status was either poor or very poor following COVID-19 illness. ConclusionsThe PCS involves almost all organ systems, regardless of the severity of acute COVID-19 illness. Two doses of vaccine help to reduce development of PCS. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSAlthough the evidence is mounting in prolonged COVID-19 symptoms among COVID-19 survivors, to date, the full range of such post-COVID-19 symptoms (PCS) is not yet fully understood. There is a lack of studies that assessed PCS comprehensively among persons who have recovered from the COVID-19illness. For example, limited data are available on psychosocial, behavioral, and oral manifestations related to PCS. Further, there is a paucity of studies that included a wide range of determinants of PCS and the association of vaccination with the development of PCS across the world. Our study is the first such study conducted among COVID-19 recovered persons who with a majority of them employed in a tertiary health care institute of north India. Added value of this studyOur study, for the first time, investigated a wide range of post-COVID-19 manifestations among COVID-19 recovered persons in organ-specific and psychosocial behavioral aspects, making this the largest categorization of PCS currently (in total 16). The study included telephonic calls to each eligible candidate which helped in ensuring the COVID-19 status at the time of the study. Since the participants either were employees in the hospital or their dependents that enhance the accuracy of reporting PCS. The most prevalent symptom was unspecific PCS (85.6%), e.g., fatigue, followed by musculoskeletal manifestations (49{middle dot}8%), Ear, Nose and Throat symptoms (47{middle dot}5%), neurological (47{middle dot}0%), cardio-respiratory (42{middle dot}4%, gastrointestinal (36{middle dot}2%), ocular symptoms (31{middle dot}9%), dermatological symptoms (31{middle dot}5%), and cardio-vascular (24{middle dot}5%) symptoms, and mental health symptoms (23{middle dot}7%). The rest of the organ specific symptoms were observed in less than 20% of the respondents. Older age, female gender, pre-existing co-morbid, oxygen supplementation during acute illness, the severity of illness, working in health care institutions were associated with PCS. Vaccination after the second dose was protective against PCS compared to non-vaccinated participants. Further, our study also reported a rating of the overall health status among COVID survivors, whereby around 8.3% of them reported being a poor or very poor health. Implications of all the available evidencePCS affects a multi-organ organ system, irrespective of the severity of acute-phase COVID-19 illness and hospitalization. Such persistent COVID-19 symptoms, compounded by its heterogeneity among COVID survivors can pose a substantial burden to the affected individuals and their families and additional challenges for healthcare delivery and public health service. The current study shows that one in three individuals experience persistent COVID-19 symptoms. Since the COVID pandemic is still ongoing across the world, therefore, the number of people experiencing PCS is likely to be increased substantially further. An integrated PCS care strategy, but not limited to organ-specific healthcare disciplines, others such as psychosocial support, including counseling and education, rehabilitation, community-based rehabilitation programs will be required for management. Prioritization of PCS care to elder and co-morbid patients should be recommended. Expediting the vaccination drive will be helpful to reduce the development of persistent COVID-19 symptoms. Research, collaborative and multidisciplinary, is required to understand the underlying pathophysiology mechanism for PCS.

Assessment of Post COVID-19 Health Problems and Its Determinants in North India: A Descriptive Cross-Sectional Study (preprint)

With millions of people getting affected with COVID-19 pandemic caused by a novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), people living with post COVID-19 symptoms (PCS) are expected to rise in the future· The present study aimed at assessing PCS comprehensively and its associated factors among COVID-19 recovered adult population in north India. Methods: In a tertiary health centre at Delhi, an online based cross-sectional study was conducted using a semi-structured questionnaire, developed by employing a nominal group technique, in aged 18 years and above who were SARS-CoV-2 positive during the month of January to April 2021. Socio-demographic, various potential risk factors, including pre-existing morbidities, vaccination status, and severity of acute COVID-19 illness, information on acute illness management and a spectrum of PCS were collected between June 16 to July 28, 2021. Each participant was contacted telephonically first, before sending the survey link. PCS were presented as relative frequency; chi-square test, odds ratio, including adjusted, were calculated to rule out association between PCS and potential predictors. Results: A total of 773 of 1801 COVID recovered participants responded to the link reaching a participation rate of 42·9%, with a median age of 34 years (IQR 27 to 44). Male respondents were 56·4%. Around 33·2% of them had PCS at four or more weeks, affecting almost all body organ systems. The most prevalent PCS were fatigue (79·3%), pain in the joins (33·4%), muscle (29·9%), hair loss (28·0%), headache (27·2%), breathlessness (25·3%), sleep disturbance (25·3%) and cough (24·9%). The prevalence of PCS was reduced to 12·8% at 12 weeks after positive test. Factor such as female gender, older age, oxygen supplementation during the acute illness, working in healthcare care facilities, the severity of acute illness, and pre-existing co-morbid were risk factors for PCS. Further, vaccination (second dose) reduced the odds of developing PCS by 45% compared to unvaccinated participants (aOR 0·65; 95%CI 0·45-0·96). Finally, 8·3% of participants rated their overall health status was either poor or very poor following COVID-19 illness. Conclusions: The PCS involves almost all organ systems, regardless of the severity of acute COVID-19 illness. Two doses of vaccine help to reduce development of PCS.Funding Information: There is no sources of funding for this study. Authors contributed voluntarily to this study.Declaration of Interests: There are no conflicts of interest.Ethics Approval Statement: The study was approved by the institute ethics committee at the institution. The participants were asked for the digital informed consent at the time of registration. The study was done in accordance with ethical principles of the Declaration of Helsinki.

High throughput detection and genetic epidemiology of SARS-CoV-2 using COVIDSeq next-generation sequencing

The rapid emergence of coronavirus disease 2019 (COVID-19) as a global pandemic affecting millions of individuals globally has necessitated sensitive and high-throughput approaches for the diagnosis, surveillance, and determining the genetic epidemiology of SARS-CoV-2. In the present study, we used the COVIDSeq protocol, which involves multiplex-PCR, barcoding, and sequencing of samples for high-throughput detection and deciphering the genetic epidemiology of SARS-CoV-2. We used the approach on 752 clinical samples in duplicates, amounting to a total of 1536 samples which could be sequenced on a single S4 sequencing flow cell on NovaSeq 6000. Our analysis suggests a high concordance between technical duplicates and a high concordance of detection of SARS-CoV-2 between the COVIDSeq as well as RT-PCR approaches. An in-depth analysis revealed a total of six samples in which COVIDSeq detected SARS-CoV-2 in high confidence which were negative in RT-PCR. Additionally, the assay could detect SARS-CoV-2 in 21 samples and 16 samples which were classified inconclusive and pan-sarbeco positive respectively suggesting that COVIDSeq could be used as a confirmatory test. The sequencing approach also enabled insights into the evolution and genetic epidemiology of the SARS-CoV-2 samples. The samples were classified into a total of 3 clades. This study reports two lineages B.1.112 and B.1.99 for the first time in India. This study also revealed 1,143 unique single nucleotide variants and added a total of 73 novel variants identified for the first time. To the best of our knowledge, this is the first report of the COVIDSeq approach for detection and genetic epidemiology of SARS-CoV-2. Our analysis suggests that COVIDSeq could be a potential high sensitivity assay for the detection of SARS-CoV-2, with an additional advantage of enabling the genetic epidemiology of SARS-CoV-2.

A survey on knowledge and awareness among Indian citizens toward application to fight against COVID-19: A cross-sectional study

Background: Coronavirus disease 2019 (COVID-19) pandemic is one of the greatest public health risks that the world has ever seen in the past 100 years. The global impact of COVID-19 pandemic has led to a rapid growth and the use of mobile health applications. Certain measures taken to prevent the spread of the disease include contact tracing, testing, and isolation. The main aim of this survey was to assess knowledge and awareness among Indian citizens toward application to fight against COVID-19. Materials and Methods: This was a cross-sectional, web-based survey conducted during the peak period of the pandemic to assess knowledge and awareness among 489 Indian citizens toward application to fight against COVID-19. Using Google Forms, an online semi-structured questionnaire with informed consent form was generated. The survey link was sent through online platforms such as WhatsApp, e-mails, and Facebook to the investigator contacts. Chi-square test was used to determine the level of association between the variables. Results: The survey results showed that out of 489 participants, 99.5% (P < 0.001) heard about COVID-19 apps. Majority of participants, that is, 84.5% and 81.8% believed that these apps helped to protect them and community from COVID-19 and helped in self-assessment test for infection mitigation, respectively. Nearly 69.9% of participants believed that the purpose of these apps was to track COVID-19 cases, to help general population to fight against COVID-19, and to prevent spread of COVID-19 cases. Almost 85.5% of participants found that Aarogya Setu app was most beneficial for them. More than half of participants, that is, 58.9% believed that these apps alert users when they come in proximity to an infected person. Conclusion: This survey demonstrates strong public support for app-based contact tracing to tackle with COVID-19 pandemic. Majority of individuals agreed that these applications are informative and helped general population in self-assessment test and contact tracing. During this distress situation and a severe shortage oftesting facilities, the self-risk assessment function available in the apps can help identify the patients at risk for COVID-19.

Efficacy of Two Siddha Poly herbal Decoctions, Nilavembu Kudineer and Kaba Sura Kudineer, along with Standard Allopathy Treatment in the Management of Mild to Moderate Symptomatic COVID-19 Patients -a Double-Blind, Placebo Controlled, Clinical Trial (preprint)

Background & Aim: Globally, the ongoing pursuit in exploring an effective drug to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has not met with significant success till date. Indian traditional medicines, especially poly herbal formulations like Nilavembu Kudineer (NVK) and Kaba Sura Kudineer (KSK) of the Siddha system of medicine have been used as public health interventions for controlling viral epidemics like dengue and Chikungunya. These traditional therapies have been found safe, effective, and widely accepted. The current study evaluates the comparative efficacy of NVK and KSK as opposed to the placebo, in the management of mild to moderate COVID-19 disease. Methods: The study was a double blind, placebo controlled comparative clinical trial, with the primary objective of determining the efficacy of KSK and NVK. Patients (n=125) diagnosed with mild to moderate COVID-19 symptoms were enrolled in the study over a period of 4 months (Aug 2020 – Dec 2020). Participants were randomised into 3 arms; placebo-decaffeinated tea in Arm 1; NVK in Arm II and KSK in Arm III. Each arm received 60 ml of the respective treatment twice a day, post morning and evening meals, along with standard Allopathy treatment for a maximum of 10 days. The main outcome measures of the study were the reduction in SARS-CoV-2 viral load, hospital stay, and time taken by the patients to become asymptomatic from symptomatic. Efficacy assessments included clinical symptoms (fever, cough and breathlessness) each day and real-time reverse transcription-polymerase chain reaction (RT-PCR),liver function test (LFT), renal function test (RFT) and electrolytes and electrocardiogram (ECG) at baseline (Day 0), Day 3, 6 and 10. Post treatment, participants were followed up for 30 days via phone for adverse effects if any. Effects of drugs on inflammatory markers (IL6,) at the end of treatment were also recorded. Adverse events (AE) were monitored throughout the study. Results: The results revealed that when compared to patients in placebo arm, those in NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and the time taken to become symptomatic from asymptomatic. Out of 125 COVID-19 patients recruited, 120 completed the study; two from the placebo group developed severe symptoms and were shifted to intensive care unit (ICU) and three patients from arms II and III withdrew from the study. The mean age of females (n=60) and males (n=60) enrolled was between 40.2 and 44.3 years respectively. Results were more promising for all the patients in NVK and KSK arms as all enrolled participants (100%) under this group got discharged by day 6 as compared to only 42.5% (n=17) from placebo groupon that day. The hospital stay time for patients in Arm I, was significantly longer (Mean [SD]=8.4 [2.0] days) as compared to the Arm II and III (Mean [SD]=4.7 [1.5] and 4.2 [1.5] days respectively (Kruskal Wallis test, p=0.0001).Patients in the three groups took a significantly different number of days to become asymptomatic. While Arm II and III patients took mean 2.5 and 1.7 days respectively, Arm I, patients took a mean of 4.2 days (Kruskal Wallis test, p=0.0001). In all, two adverse events were recorded, one for vomiting and one for diarrhoea lasting a day in Arm I & Arm II respectively. Mean value of interleukin-6 (IL6) was significantly different in comparison to the placebo-decaffeinated tea arm (NVK=2.6 and KSK=2.2, Placebo=4.0, p=0.02).The other blood biochemical parameters like C-Reactive Protein (CRP), Lactate Dehydrogenase (LDH), Ferritin and D-Dimer that were analysed at the baseline and at the time of discharge from hospital, were not significantly different in the three arms. Conclusion: NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2 and time taken for patients to become asymptomatic from symptomatic, when compared to the placebo (decaffeinated tea).The primary outcome measures of KSK arm were significantly better than that in the NVK arm. 

Tele-Rehabilitation for People with Visual Disabilities During COVID-19 Pandemic: Lesson Learned (preprint)

BackgroundThe COVID-19 outbreak poses a global crisis in health care delivery system, including habilitation and rehabilitation services. In the present study, we shared our experiences on telerehabilitation services established primarily for students with visual disabilities (SwVD) amidst COVID-19 pandemic and its outputs. MethodsFollowing the lockdown declared on March 23, 2020, the rehabilitative team of a tertiary eye center in north India received information that many VCS were stranded in schools for the blind in Delhi, and feeling with anxiety and panic in absence of teachers. Shortly, the room for vision rehabilitation clinic was set-up for tele-facilities. The intended services was explained while disseminating the mobile numbers. A semi-structured questionnaire consisting of closed and open-ended was developed to record COVID-19 knowledge and concerns. Inductive content analysis was used to report the qualitative information. ResultsAs of June 30, 2020, a total of 492 clients contacted the team, with maximum from Delhi (41.5%), and predominantly males (78.8%). Around 80.3% of callers were VCS with age range of 11 to 30 years. The two most frequently encountered health needs were itching in eyes (36.1%) and headache (29%). Television news was the most used medium among callers to get COVID-19 information. Cough is a less frequently known mode of transmission (28%), similarly handwashing as a less known for prevention (17.2%). Eight concerns were recorded based on qualitative data analysis. ConclusionTele-rehabilitation provides valuable insights and has the potential to address various concerns, uncertainty, anxiety, and fear among SVD during the pandemic.

High throughput detection and genetic epidemiology of SARS-CoV-2 using COVIDSeq next generation sequencing (preprint)

The rapid emergence of coronavirus disease 2019 (COVID-19) as a global pandemic affecting millions of individuals globally has necessitated sensitive and high-throughput approaches for the diagnosis, surveillance and for determining the genetic epidemiology of SARS-CoV-2. In the present study, we used the COVIDSeq protocol, which involves multiplex-PCR, barcoding and sequencing of samples for high-throughput detection and deciphering the genetic epidemiology of SARS-CoV-2. We used the approach on 752 clinical samples in duplicates, amounting to a total of 1536 samples which could be sequenced on a single S4 sequencing flow cell on NovaSeq 6000. Our analysis suggests a high concordance between technical duplicates and a high concordance of detection of SARS-CoV-2 between the COVIDSeq as well as RT-PCR approaches. An in-depth analysis revealed a total of six samples in which COVIDSeq detected SARS-CoV-2 in high confidence which were negative in RT-PCR. Additionally, the assay could detect SARS-CoV-2 in 21 samples and 16 samples which were classified inconclusive and pan-sarbeco positive respectively suggesting that COVIDSeq could be used as a confirmatory test. The sequencing approach also enabled insights into the evolution and genetic epidemiology of the SARS-CoV-2 samples. The samples were classified into a total of 3 clades. This study reports two lineages B.1.112 and B.1.99 for the first time in India. This study also revealed 1,143 unique single nucleotide variants and added a total of 73 novel variants identified for the first time. To the best of our knowledge, this is the first report of the COVIDSeq approach for detection and genetic epidemiology of SARS-CoV-2. Our analysis suggests that COVIDSeq could be a potential high sensitivity assay for detection of SARS-CoV-2, with an additional advantage of enabling genetic epidemiology of SARS-CoV-2.