Modifying lignin composition and xylan O-acetylation induces changes in cell wall composition, extractability, and digestibility.

BACKGROUND: Lignin and xylan are important determinants of cell wall structure and lignocellulosic biomass digestibility. Genetic manipulations that individually modify either lignin or xylan structure improve polysaccharide digestibility. However, the effects of their simultaneous modifications have not been explored in a similar context. Here, both individual and combinatorial modification in xylan and lignin was studied by analysing the effect on plant cell wall properties, biotic stress responses and integrity sensing. RESULTS: Arabidopsis plant co-harbouring mutation in FERULATE 5-HYDROXYLASE (F5H) and overexpressing Aspergillus niger acetyl xylan esterase (35S:AnAXE1) were generated and displayed normal growth attributes with intact xylem architecture. This fah1-2/35S:AnAXE1 cross was named as hyper G lignin and hypoacetylated (HrGHypAc) line. The HrGHypAc plants showed increased crystalline cellulose content with enhanced digestibility after chemical and enzymatic pre-treatment. Moreover, both parents and HrGHypAc without and after pre-treating with glucuronyl esterase and alpha glucuronidase exhibited an increase in xylose release after xylanase digestion as compared to wild type. The de-pectinated fraction in HrGHypAc displayed elevated levels of xylan and cellulose. Furthermore, the transcriptomic analysis revealed differential expression in cell wall biosynthetic, transcription factors and wall-associated kinases genes implying the role of lignin and xylan modification on cellular regulatory processes. CONCLUSIONS: Simultaneous modification in xylan and lignin enhances cellulose content with improved saccharification efficiency. These modifications loosen cell wall complexity and hence resulted in enhanced xylose and xylobiose release with or without pretreatment after xylanase digestion in both parent and HrGHypAc. This study also revealed that the disruption of xylan and lignin structure is possible without compromising either growth and development or defense responses against Pseudomonas syringae infection.

Selection of appropriate reference genes for normalization of qRT-PCR based gene expression analysis in SARS-CoV-2, and Covid-associated Mucormycosis infection

Selection of reference genes in quantitative PCR is critical to determine accurate and reliable mRNA expression. Despite this knowledge, not a single study has investigated the expression stability of housekeeping genes to determine their suitability to act as reference gene in SARS-CoV-2 or Covid19 associated mucormycosis (CAM) infections. Herein, we address these gaps by investigating the expression stability of nine most commonly used housekeeping genes including TBP, CypA, B2M, 18S, PGC-1, GUSB, HPRT-1, {beta}-ACTIN and GAPDH in the patients of varying severity (asymptomatic, mild, moderate and severe). We observed significant differences in the expression of candidate genes across the disease spectrum. Next, using various statistical algorithms (delta Ct, Normfinder, Bestkeeper, RefFinder and GeNorm), we observed that CypA demonstrated the most consistent expression across the patients of varying severity and emerged as the most suitable gene in Covid19, and CAM infections. Incidentally, the most commonly used reference gene GAPDH showed maximum variations and found to be the least suitable. Lastly, comparative evaluation of expression of NRF2 is performed following normalization with GAPDH and CypA to highlight the relevance of an appropriate reference gene. Our results reinforce the idea of a selection of housekeeping genes only after validation especially during infections.

Adolescents Hospitalized with SARS-CoV-2: Analysis of Clinical Profile and Risk Factors for Severe Disease over a two-year period

IntroductionThere is a lack of studies in adolescents with COVID-19 from developing countries. We aimed to describe the clinical profile and risk factors for severe disease in adolescents hospitalized with COVID-19. MethodsA retrospective analysis of a prospectively admitted cohort of COVID-19 patients was performed at a tertiary hospital in north India. Adolescents aged 12 to 18 years who were hospitalized during the first wave (March 2020 to December 2020) and the second wave (March 2021 to June 2021) of the pandemic were included. Data on the demographic details, clinical presentation, laboratory parameters, disease severity at admission, treatments received, and in-hospital outcomes were retrieved and logistic regression was used to identify the risk factors for occurrence of moderate or severe disease. ResultsThe study included 197 adolescents with median (IQR) age 15 (13-17) years, of whom 117 (59.4%) were male. Among these, 170 (86.3%) were admitted during the 1st wave. Underlying comorbidities were present in 9 (4.6%) patients. At the time of hospital admission, 60 (30.9%) patients were asymptomatic. In the severity grading, 148 (84.6%) had mild, 16 (9.1%) had moderate, and 11 (6.3%) had severe disease. Fever (14.9%) and cough (14.9%) were the most commonly encountered symptoms. The median (IQR) duration of hospital stay was 10 (8-13) days and 6 (3.1%) patients died in hospital. The odds of moderate to severe disease were 3.8 for second wave, 1.9 for fever and 1.1 for raised C reactive protein (CRP). ConclusionIn our single-center study from northern India, adolescents admitted with COVID-19 had predominantly asymptomatic or mild disease. Admission during the second wave of COVID-19 pandemic, presence of fever and raised CRP were risk factors for moderate or severe disease. Lay SummaryFrom 3rd January 2022 onwards, adolescents between 15 to 18 years of age in India will be given Covaxin vaccine, as per the latest Indian government guidelines. In our study, we aimed to describe the clinical profile and risk factors for severe disease in adolescents hospitalized with COVID-19. Our study included 197 adolescents. 170 (86.3%) of them were admitted during the 1st wave and the rest 27 (13.7%) during the 2nd wave. At the time of hospital admission, 60 (30.9%) patients were asymptomatic. In the severity grading, 148 (84.6%) had mild, 16 (9.1%) had moderate, and 11 (6.3%) had severe disease. Fever (14.9%) and cough (14.9%) were the most commonly encountered symptoms. The median (IQR) duration of hospital stay was 10 (8-13) days and 6 (3.1%) patients died in hospital. 2nd wave, fever and high C reactive protein increased the odds of moderate to severe disease.

In-hospital mortality due to breakthrough COVID-19 among recipients of COVISHIELD (ChAdOx nCoV-19) and COVAXIN (BBV152)

BackgroundMultiple vaccines have received emergency-use authorization in different countries in the fight against the COVID-19 pandemic. India had started its vaccination campaign using the COVISHIELD (ChAdOx nCoV-19) and the COVAXIN (BBV152) vaccines. However, there is a lack of head-to-head comparisons of the different vaccines. MethodsWe performed a retrospective cohort study during the second wave of the pandemic in India with predominant circulation of the delta strain of SARS-CoV-2. We enrolled adult patients who were hospitalized with breakthrough COVID-19 infection after vaccination. We compared in-hospital outcomes between patients who had received the COVISHIELD (n=181) or COVAXIN vaccines. ResultsBetween April and June 2021, a total of 353 patients were enrolled, among whom 181 (51.3%) received COVAXIN (156 partially vaccinated and 25 fully vaccinated) and 172 (48.7%) received COVISHIELD (155 partially vaccinated and 17 fully vaccinated). The in-hospital mortality did not differ between the recipients of COVISHIELD or COVAXIN in either the fully vaccinated [2 deaths (11.8%) vs 0 deaths (0%), respectively p=0.08] or the partially vaccinated cohorts [31 deaths (20%) vs 28 deaths (17.9%), respectively, p=0.65]. ConclusionsPatients who are hospitalized with breakthrough COVID-19 had similar in-hospital outcome irrespective of whether they received COVISHIELD or COVAXIN.

The effectiveness of SARS-CoV-2 vaccination in preventing severe illness and death- real-world data from a cohort of patients hospitalized with COVID-19.

BackgroundDue to the unprecedented speed of SARS-CoV-2 vaccine development, their efficacy trials and issuance of emergency use approvals and marketing authorizations, additional scientific questions remain that need to be answered regarding vaccine effectiveness, vaccination regimens and the need for booster doses. While long-term studies on the correlates of protection, vaccine effectiveness, and enhanced surveillance are awaited, studies on breakthrough infections help us understand the nature and course of this illness among vaccinated individuals and guide in public health preparedness. MethodsThis observational cohort study aimed at comparing the differences in clinical, biochemical parameters and the hospitalization outcomes of 53 fully vaccinated individuals with those of unvaccinated (1,464) and partially vaccinated (231) individuals, among a cohort of 2,080 individuals hospitalized with SARS-CoV-2 infection. ResultsCompleting the course of vaccination protected individuals from developing severe COVID-19 as evidence by lower proportions of those with hypoxia, abnormal levels of inflammatory markers, requiring ventilatory support and death compared to unvaccinated and partially vaccinated individuals. There were no differences in these outcomes among patients who received either vaccine type approved in India. ConclusionWith a current rate of only 9.5% of the Indian population being fully vaccinated, efforts should be made to improve the vaccination rates as a timely measure to prepare for the upcoming waves of this highly transmissible pandemic. Vaccination rates of the communities may also guide in the planning of the health needs and appropriate use of medical resources. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe Government of India started vaccinating its citizens from the 16th of January 2021, after emergency use authorization had been received for the use of two vaccines, BBV152, a COVID-19 vaccine based on the whole-virion SARS-CoV-2 vaccine strain NIV-2020-770, (Covaxin) and the recombinant replication-deficient chimpanzee adenovirus vector encoding the spike protein ChAdOx1 nCoV-19 Corona Virus Vaccine (Covishield). These have been approved by the Indian regulatory authority based on randomized controlled studies. In these studies, was found that the vaccines led to more than 90% reduction in symptomatic COVID-19 disease. However, there is scarce evidence of the efficacy of these vaccines in real-world scenarios. A few studies have looked at vaccinated cohorts such as health care workers in whom the vaccines had an efficacy similar to the RCTs. In a study of patients with SARS-CoV-2 infection admitted to a tertiary care hospital in New Delhi, it was found that mortality in fully vaccinated patients was 12.5% as compared to 31.5% in the unvaccinated cohort. Added-value of this studyThis cohort of hospitalized patients with SARS-CoV-2 infection was studied during the peak of the second wave of COVID-19 in India during which the delta variant of concern was the predominant infecting strain and had 26% patients who were partially vaccinated and 71.4% who were unvaccinated. Only 3% of the patients were fully vaccinated and developed a breakthrough infection. At the time of presentation, 13% of the individuals with breakthrough infection and 48{middle dot}5% in the non-vaccinated group were hypoxic. Inflammatory markers were significantly lower in the completely vaccinated patients with breakthrough infection. The need for use of steroids and anti-viral agents such as remdesivir was also significantly low in the breakthrough infection group. A significantly less proportion of the individuals with breakthrough infection required oxygen supplementation or ventilatory support. Very few deteriorated or progressed to critical illness during their hospital stay. Only 3 individuals (5.7%) out of the 53 who developed breakthrough infection succumbed to illness while case fatality rates were significantly higher in the unvaccinated (22.8%) and partially vaccinated (19.5%) groups. Propensity score weighted multivariate logistic regression analysis revealed lower odds of developing hypoxia, critical illness or death in those who were completely vaccinated. Implications of all the available evidenceThe real-world effectiveness of the vaccines against SARS-CoV-2 seems to be similar to the randomized controlled trials. The vaccines are very effective in reducing the incidence of severe COVID-19, hypoxia, critical illness and death. The reduced need for oxygen supplementation, mechanical ventilation and the requirement of corticosteroids or other expensive medications such as anti-viral drugs could go a long way in redistributing scarce health care resources. All nations must move forward and vaccinate the citizens, as the current evidence suggests that prevention is better than cure.

Silent Hypoxia in Coronavirus disease-2019: Is it more dangerous?-A retrospective cohort study

BackgroundHypoxia in patients with COVID-19 is one of the strongest predictors of mortality. Silent hypoxia is characterized by the presence of hypoxia without dyspnea.. Silent hypoxia has been shown to affect the outcomes in previous studies. Research QuestionAre the outcomes in patients presenting with silent hypoxia different from those presenting with dyspneic hypoxia? Study design and MethodsThis was a retrospective study of a cohort of patients with SARS-CoV-2 infection who were hypoxic at presentation. Clinical, laboratory, and treatment parameters in patients with silent hypoxia and dyspneic hypoxia were compared. Multivariate logistic regression models were fitted to identify the factors predicting mortality. ResultsAmong 2080 patients with COVID-19 admitted to our hospital, 811 patients were hypoxic with SpO2<94% at the time of presentation. 174 (21.45%) did not have dyspnea since the onset of COVID-19 symptoms. 5.2% of patients were completely asymptomatic for COVID-19 and were found to be hypoxic only on pulse oximetry. The case fatality rate in patients with silent hypoxia was 45.4% as compared to 40.03% in dyspneic hypoxic patients (P=0.202). The odds ratio of death was 1.1 (95% CI 0.41-2.97) in the patients with silent hypoxia after adjusting for baseline characteristics, laboratory parameters, treatment, and in-hospital complications, which did not reach statistical significance (P=0.851). InterpretationSilent hypoxia may be the only presenting feature of COVID-19. Since the case fatality rate is comparable between silent and dyspneic hypoxia, it should be recognized early and treated as aggressively. Since home isolation is recommended in patients with COVID-19, it is essential to use pulse oximetry at the home setting to identify these patients.

Clinical features, demography and predictors of outcomes of SARS-CoV-2 infection in a tertiary care hospital in India-A cohort study

BackgroundThe second wave of the COVID-19 pandemic hit India from early April 2021 to June 2021 and more than 400,000 cases per day were reported in the country. We describe the clinical features, demography, treatment trends, baseline laboratory parameters of a cohort of patients admitted at the All India Institute of Medical Sciences, New Delhi with SARS-CoV-2 infection and their association with the outcome. MethodsThis was a retrospective cohort study describing the clinical, laboratory and treatment patterns of consecutive patients admitted with SARS-CoV-2 infection. Multivariate logistic regression models were fitted to identify the clinical and biochemical predictors of developing hypoxia, deterioration during the hospital stay and death. FindingsA total of 2080 patients were included in the study. The case fatality rate was 19.5%. Amongst the survivors, the median duration of hospital stay was 8 (5-11) days. Out of 853 (42.3%%) of patients who had COVID-19 Acute respiratory distress syndrome at presentation, 340 (39.9%) died. Patients aged 45-60 years [OR (95% CI): 1.8 (1.2-2.6)p =0.003] and those aged >60 years [OR (95%CI): 3.4 (2.3-5.2), p<0.001] had a higher odds of death as compared to the 18-44 age group. Vaccination reduced the odds of death by 30% [OR (95% CI): 0.7 (0.5-0.9), p=0.036]. Patients with hyper inflammation at baseline as suggested by leucocytosis [OR (95% CI): 2.1 (1.4-3.10), p <0.001], raised d-dimer >500 mg/dL [OR (95% CI): 3.2 (2.2-4.6), p <0.001] and raised C-reactive peptide >0.5 mg/L [OR (95% CI): 3.8 (1.1-13), p=0.037] had higher odds of death. Patients who were admitted in the second week had lower odds of death and those admitted in the third week had higher odds of death. InterpretationThis is the largest cohort of patients admitted with COVID-19 from India reported to date and has shown that vaccination status and early admission during the inflammatory phase can change the course of illness of these patients. Strategies should be made to improve vaccination rates and early admission of patients with moderate and severe COVID-19 to improve outcomes. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe COVID-19 pandemic has been ravaging the world since December 2019 and the cases in various regions are being reported in waves. We found that the case fatality rates ranging from 1.4% to 28.3% have been reported in the first wave in India. Older age and the presence of comorbidities are known predictors of mortality. There are no reports regarding the effectiveness of vaccination, correlation of mortality with the timing of admission to the health care facility and inflammatory markers in the second wave of the COVID-19 pandemic in India. Added-value of this studyThis study reports the real-world situation where patients get admitted at varying time points of their illness due to the mismatch between the availability of hospital beds and the rising number of COVID-19 patients during the pandemic. It reports the odds of developing severe hypoxia necessitating oxygen therapy and death thus helping identify priority groups for admission. Implications of all the available evidenceThis study found increased odds of requiring oxygen support or death in patients older than 45 years of age, with comorbidities, and those who had hyper-inflammation with raised C-reactive peptide, d-dimer or leukocytosis. Patients who were admitted in the second week of illness had lower odds of death as compared to those admitted in the third week implying that treatment with corticosteroids in the second week of the illness during the inflammatory phase could lead to reduced mortality. These findings would help triage patients and provide guidance for developing admission policy during times where hospital beds are scarce. Vaccination was found to reduce the odds of deterioration or death and should be fast-tracked to prevent further waves of the pandemic.

Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma

Background@#Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort. @*Methods@#This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and the @*results@#were analyzed. Results: Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed. @*Conclusions@#Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma

Background@#Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort. @*Methods@#This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and the @*results@#were analyzed. Results: Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed. @*Conclusions@#Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

Low Dose Radiation Therapy for COVID-19 Pneumonia: A Pilot Study

BackgroundThe World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) as pandemic in March 2020. Currently there is no vaccine or specific effective treatment for COVID-19. The major cause of death in COVID-19 is severe pneumonia leading to respiratory failure. Radiation in low doses (<100 cGy) has been known for its anti-inflammatory effect and therefore, low dose radiation therapy (LDRT) to lungs can potentially mitigate the severity of pneumonia and reduce mortality. We conducted a pilot trial to study the feasibility and clinical efficacy of LDRT to lungs in the management of patients with COVID-19. MethodsFrom June to Aug 2020, we enrolled 10 patients with COVID-19 having moderate to severe risk disease [National Early Warning Score (NEWS) of [≥]5]. Patients were treated as per the standard COVID-19 management guidelines along with LDRT to both lungs with a dose of 70cGy in single fraction. Response assessment was done based on the clinical parameters using the NEWS. ResultsAll patients completed the prescribed treatment. Nine patients had complete clinical recovery mostly within a period ranging from 3-7 days. One patient, who was a known hypertensive, showed clinical deterioration and died 24 days after LDRT. No patients showed the signs of acute radiation toxicity. ConclusionResults of our study (90% response rate) suggest the feasibility and clinical effectiveness of LDRT in COVID-19 patients having moderate to severe risk disease. This mandates a randomized controlled trial to establish the clinical efficacy of LDRT in COVID-19 pneumonia.

SARS-CoV-2 RT-PCR profile in 298 Indian COVID-19 patients : a retrospective observational study

BackgroundDespite being in the 5th month of pandemic, knowledge with respect to viral dynamics, infectivity and RT-PCR positivity continues to evolve. AimTo analyse the SARS CoV-2 nucleic acid RT-PCR profiles in COVID-19 patients. DesignIt was a retrospective, observational study conducted at COVID facilities under AIIMS, New Delhi. MethodsPatients admitted with laboratory confirmed COVID-19 were eligible for enrolment. Patients with incomplete details, or only single PCR tests were excluded. Data regarding demographic details, comorbidities, treatment received and results of SARS-CoV-2 RT-PCR performed on nasopharyngeal and oropharyngeal swabs, collected at different time points, was retrieved from the hospital records. Results298 patients were included, majority were males (75{middle dot}8%) with mean age of 39{middle dot}07 years (0{middle dot}6-88 years). The mean duration from symptom onset to first positive RT-PCR was 4{middle dot}7 days (SD 3{middle dot}67), while that of symptom onset to last positive test was 17{middle dot}83 days (SD 6{middle dot}22). Proportions of positive RT-PCR tests were 100%, 49%, 24%, 8{middle dot}7% and 20{middle dot}6% in the 1st, 2nd, 3rd, 4th & >4 weeks of illness. 12 symptomatic patients had prolonged positive test results even after 3 weeks of symptom onset. Age >= 60 years was associated with prolonged RT-PCR positivity (statistically significant). ConclusionThis study showed that the average period of PCR positivity is more than 2 weeks in COVID-19 patients; elderly patients have prolonged duration of RT-PCR positivity and requires further follow up.

Management of mild COVID-19: Policy implications of initial experience in India

ObjectivesOngoing pandemic due to COVID-19 has spread across countries, surprisingly with variable clinical characteristics and outcomes. This study was aimed at describing clinical characteristics and outcomes of admitted patients with mild COVID-19 illness in the initial phase of pandemic in India. DesignRetrospective (observational) study. SettingCOVID facilities under AIIMS, New Delhi, where, isolation facilities were designed to manage patients with mild illness and dedicated COVID ICUs was created to cater patients with moderate to severe illness. ParticipantsPatients aged 18 years or more, with confirmed illness were eligible for enrolment. Patients who were either asymptomatic or mildly ill at presentation were included. Patients with moderate to severe illness at admission, or incomplete clinical symptomatology records were excluded. MethodsData regarding demographic profile, comorbidities, clinical features, hospital course, treatment, details of results of RT-PCR for SARS-CoV-2 done at baseline and at day 14, chest radiographs (wherever available) as well as laboratory parameters was obtained retrospectively from the hospital records. Main outcome measuresFinal outcome was noted in terms of course of the disease, patients discharged, still admitted (at time of conclusion of study) or death. ResultsOut of 231 cases included, majority were males(78{middle dot}3%) with a mean age of 39{middle dot}8 years. Comorbidities were present in 21{middle dot}2% of patients, diabetes mellitus and hypertension being most common. The most common symptoms were dry cough(81, 35%), fever(64, 27{middle dot}7%), sore throat(36, 15{middle dot}6%), and dyspnoea(24, 10{middle dot}4%); asymptomatic infection was noted in 108(46.8%) patients. Presence of comorbidities was an independent predictor of symptomatic disease (OR- 2{middle dot}66; 95% CI 1{middle dot}08 to 6{middle dot}53, p= 0{middle dot}03). None of the patients progressed to moderate to severe COVID-19. There were no deaths in this cohort. ConclusionsPatients with mild disease at presentation had a stable disease course and therefore such cases can be managed outside hospital setting. A large proportion of patients remained asymptomatic throughout the course of infection and those with comorbidities are more likely to be symptomatic. Trial registrationNot applicable

Transmission dynamics of the COVID-19 epidemic in India, and evaluating the impact of asymptomatic carriers and role of expanded testing in the lockdown exit strategy: a modelling approach

BackgroundThe SARS-CoV-2 pandemic has quickly become an unprecedented global health threat. India with its unique challenges in fighting this pandemic, imposed one of the worlds strictest and largest population-wide lockdown on 25 March 2020. Here, we estimated key epidemiological parameters and evaluated the effect of control measures on the COVID-19 epidemic in India. Through a modelling approach, we explored various strategies to exit the lockdown. MethodsWe obtained data from 140 confirmed COVID-19 patients at a tertiary care hospital in India to estimate the delay from symptom onset to confirmation and the proportion of cases without symptoms. We estimated the basic reproduction number (R0) and time-varying effective reproduction number (Rt) after adjusting for imported cases and reporting lag, using incidence data from 4 March to 25 April 2020 for India. We built upon the SEIR model to account for underreporting, reporting delays, and varying asymptomatic proportion and infectivity. Using this model, we simulated lockdown relaxation under various scenarios to evaluate its effect on the second wave, and also modelled increased detection through testing. We hypothesised that increased testing after lockdown relaxation will decrease the epidemic growth enough to allow for greater resumption of normal social mixing thus minimising the social and economic fallout. ResultsThe median delay from symptom onset to confirmation (reporting lag) was estimated to be 2{middle dot}68 days (95%CI 2{middle dot}00-3{middle dot}00) with an IQR of 2{middle dot}03 days (95%CI 1{middle dot}00-3{middle dot}00). 60{middle dot}7% of confirmed COVID-19 cases (n=140) were found to be asymptomatic. The R0 for India was estimated to be 2{middle dot}083 (95%CI 2{middle dot}044-2{middle dot}122; R2 = 0{middle dot}972), while the Rt gradually down trended from 1{middle dot}665 (95%CI 1{middle dot}539-1{middle dot}789) on 30 March to 1{middle dot}159 (95%CI 1{middle dot}128-1{middle dot}189) on 22 April. In the modelling, we observed that the time lag from date of lockdown relaxation to start of second wave increases as lockdown is extended farther after the first wave peak. This benefit was greater for a gradual relaxation as compared to a sudden lifting of lockdown. We found that increased detection through testing decreases the number of total infections and symptomatic cases, and the benefit of detecting each extra case was higher when prevailing transmission rates were higher (as when restrictions are relaxed). Lower levels of social restrictions when coupled with increased testing, could achieve similar outcomes as an aggressive social distancing regime where testing was not increased. ConclusionsThe aggressive control measures in India since 25 March have produced measurable reductions in transmission, although suppression needs to be maintained to achieve sub-threshold Rt. Additional benefits for mitigating the second wave can be achieved if lockdown can be feasibly extended farther after the peak of active cases has passed. Aggressive measures like lockdowns may inherently be enough to suppress the epidemic, however other measures need to be scaled up as lockdowns are relaxed. Expanded testing is expected to play a pivotal role in the lockdown exit strategy and will determine the degree of return to normalcy that will be possible. Increased testing coverage will also ensure rapid feedback from surveillance systems regarding any resurgence in cases, so that geo-temporally targeted measures can be instituted at the earliest. Considering that asymptomatics play an undeniable role in transmission of COVID-19, it may be prudent to reduce the dependence on presence of symptoms for implementing control strategies, behavioral changes and testing.

Acute Phase Proteins as Predictors of Survival in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease Requiring Mechanical Ventilation.

Few studies have tried to assess prognostic variables in chronic obstructive pulmonary disease (COPD) patients requiring mechanical ventilation (MV). We evaluated serum C reactive protein, (CRP) pre-albumin (PA) and transferrin (TR) levels in AE-COPD patients requiring MV as prognostic markers of in hospital mortality. 93 AE-COPD patients on MV were evaluated. Detailed clinical evaluation was done daily. Serum CRP & PA were measured on admission, 3rd, 8th and 16th day; TR was measured on admission, 8th and 16th day. Demographics, baseline parameters, CRP, PA and TR were correlated with mortality. Of 93 patients, 49 (52.69%) survived whereas 44 patients (47.31%) died. APACHE II, serum urea & albumin were similar in survivors & non-survivors. Baseline CRP (≥10.5 mg/dl) had sensitivity of 60.5%, specificity of 60.2%, with area under curve (AUC) of 0.62 as predictor of mortality. CRP (≥7 mg/dl) on day 3 had sensitivity (65.5%) and specificity (63.3%) with AUC 0.70 as predictor of mortality. Baseline serum prealbumin was 11.00 (0.09-29.26) mg/dl, and similar in survivors & non-survivors (p = 0.7). Prealbumin at day 8 (n = 50) < 13.5 mg/dl had sensitivity 54.6%, and specificity 51.4% with AUC 0.54 (95% CI 0.34-0.75) as predictor of mortality. Transferrin at day 8 (n = 50) of <148.9 had sensitivity 63.4% and specificity 61.4% with AUC 0.61 with respect to mortality. High CRP levels at baseline, persistently elevated CRP (on day 3) may predict mortality in AE-COPD patients requiring MV. Further studies are required to establish prognostic variables in this patient population.

Quality of life measures in lung cancer.

Lung cancer is one of the leading causes of cancer death worldwide. Survival has not improved significantly in spite of newer therapies. In view of the high-symptom burden and severe morbidity, evaluation of quality of life (QOL) becomes important in these patients. Several instruments are now available for this purpose, and have demonstrated good correlation with performance status, symptoms, and survival. Quality of life assessments also help in comparing different therapeutic regimes, thus allowing selection of the appropriate modality. Problems of inconsistent interpretability and high-patient dropout rate poses a challenging problem that needs to be tackled. In spite of these drawbacks, QOL is now considered to be an essential component of lung cancer management and should be performed routinely. Such a practice will help the physician plan appropriate treatment strategies and set practical therapeutic goals.