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Brief AbstractWe analysed SARS-CoV-2 surveillance and contact tracing data from Karnataka, India up to 21 July 2020. We estimated metrics of infectiousness and the tendency for superspreading (overdispersion), and evaluated potential determinants of infectiousness and symptomaticity in COVID-19 cases. Among 956 cases confirmed to be forward-traced, 8.7% of index cases had 14.4% of contacts but caused 80% of all secondary cases, suggesting significant heterogeneity in individual-level transmissibility of SARS-CoV-2 which could not be explained by the degree of heterogeneity in underlying number of contacts. Secondary attack rate was 3.6% among 16715 close contacts. Transmission was higher when index case was aged >18 years, or was symptomatic (adjusted risk ratio, aRR 3.63), or was lab-confirmed [≥]4 days after symptom onset (aRR 3.01). Probability of symptomatic infection increased with age, and symptomatic infectors were 8.16 times more likely to generate symptomatic secondaries. This could potentially cause a snowballing effect on infectiousness and clinical severity across transmission generations; further studies are suggested to confirm this. Mean serial interval was 5.4 days. Adding backward contact tracing and targeting control measures to curb super-spreading may be prudent. Due to low symptomaticity and infectivity, interventions aimed at children might have a relatively small impact on reducing transmission. Structured AbstractO_ST_ABSBackgroundC_ST_ABSIndia has experienced the second largest outbreak of COVID-19 globally, yet there is a paucity of studies analysing contact tracing data in the region. Such studies can elucidate essential transmission metrics which can help optimize disease control policies. MethodsWe analysed contact tracing data collected under the Integrated Disease Surveillance Programme from Karnataka, India between 9 March and 21 July 2020. We estimated metrics of disease transmission including the reproduction number (R), overdispersion (k), secondary attack rate (SAR), and serial interval. R and k were jointly estimated using a Bayesian Markov Chain Monte Carlo approach. We evaluated the effect of age and other factors on the risk of transmitting the infection, probability of asymptomatic infection, and mortality due to COVID-19. FindingsUp to 21 July, we found 111 index cases that crossed the super-spreading threshold of [≥]8 secondary cases. R and k were most reliably estimated at R 0.75 (95% CI, 0.62-0.91) and k 0.12 (0.11-0.15) for confirmed traced cases (n=956); and R 0.91 (0.72-1.15) and k 0.22 (0.17-0.27) from the three largest clusters (n=394). Among 956 confirmed traced cases, 8.7% of index cases had 14.4% of contacts but caused 80% of all secondary cases. Among 16715 contacts, overall SAR was 3.6% (3.4-3.9) and symptomatic cases were more infectious than asymptomatic cases (SAR 7.7% vs 2.0%; aRR 3.63 [3.04-4.34]). As compared to infectors aged 19-44 years, children were less infectious (aRR 0.21 [0.07-0.66] for 0-5 years and 0.47 [0.32-0.68] for 6-18 years). Infectors who were confirmed [≥]4 days after symptom onset were associated with higher infectiousness (aRR 3.01 [2.11-4.31]). Probability of symptomatic infection increased with age, and symptomatic infectors were 8.16 (3.29-20.24) times more likely to generate symptomatic secondaries. Serial interval had a mean of 5.4 (4.4-6.4) days with a Weibull distribution. Overall case fatality rate was 2.5% (2.4-2.7) which increased with age. ConclusionWe found significant heterogeneity in the individual-level transmissibility of SARS-CoV-2 which could not be explained by the degree of heterogeneity in the underlying number of contacts. To strengthen contact tracing in over-dispersed outbreaks, testing and tracing delays should be minimised, retrospective contact tracing should be considered, and contact tracing performance metrics should be utilised. Targeted measures to reduce potential superspreading events should be implemented. Interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission owing to their low symptomaticity and infectivity. There is some evidence that symptomatic cases produce secondary cases that are more likely to be symptomatic themselves which may potentially cause a snowballing effect on infectiousness and clinical severity across transmission generations; further studies are needed to confirm this finding. FundingGiridhara R Babu is funded by an Intermediate Fellowship by the Wellcome Trust DBT India Alliance (Clinical and Public Health Research Fellowship); grant number: IA/CPHI/14/1/501499.
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AimTo determine if the d-dimer levels are elevated in individuals with COVID 19 having worse clinical outcomes including all-cause mortality, ICU admission or ARDS MethodsWe conducted a systematic review and meta-analysis of published literature in Pubmed, Embase and Cochrane database through April 9, 2020 for studies evaluating the d-dimer levels in patients with and without a worse clinical outcome (all-cause mortality, ICU admission and ARDS). A total of 6 studies included in the meta-analysis. ResultsThe values of d-dimer were found to be significantly increased in patients with the composite clinical end point than in those without (SMD, 1.67 ug/ml (95% CI, 0.72-2.62 ug/ml). The SMD of the studies (Tang et al, Zhou et al, Chen et al), which used only mortality as an outcome measure was 2.5 ug/mL (95% CI, 0.62-4.41). ConclusionThe results of this concise meta-analysis suggest that d-dimer is significantly increased in patients having a worse clinical outcome (all-cause mortality, ICU admission or ARDS).
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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.
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After SARS-CoV-2 set foot in India, the Government took a number of steps to limit the spread of the disease in the country. This study involves assessing how the disease affected the population in the initial days of the epidemic. Data was collected from government-controlled and crowdsourced websites and analyzed. Studying age and sex parameters of 413 Indian COVID-19 patients, the median age of the affected individuals was found to be 36 years (IQR, 25-54) with 20-39 years males being the most affected group. The number of affected males (66.34%) was more than that of the females (33.66%). Using Susceptible-Infected-Removed (SIR) model, the range of contact rate ({beta}) of India was calculated and the role of public health interventions was assessed. If current contact rate continues, India may have 5583 to 13785 active cases at the end of 21 days lockdown. Article Summary LineThe study gives the epidemiological characteristics of the SARS-CoV-2 epidemic in India, where unlike other countries, the 20-39 years males are most affected, and the SIR model predicts the probable number of cases of COVID-19 by the end of the 21 days lockdown in the country, which will help to develop appropriate public health interventions to control the COVID-19 epidemic.
