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BackgroundSeroprevalence of IgG antibodies against SARS-CoV-2 is an important tool to estimate true burden of infection in a given population. Serosurveys, though being conducted in different parts of India, are not readily published in entirety and often do not report on the different characteristics of the population studied. In this present study, we aimed to serially estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody over 11 months at one of the largest government hospital in India. MethodIn this cross-sectional study which was conducted between between 9th June 2020 and 27th April 2021, consecutive patients admitted to medicine wards or intensive care units, who were negative for SARS-CoV-2 by RT-PCR or CBNAAT were included. The 2linic-demographic features of the subjects were recorded in pre-formed questionnaires. Anti-SARS-CoV2 antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the ELISA method. ResultsA total of 916 patients were recruited over 11 months with mean age({+/-}SD) 39.79{+/-}14.9 of years and 55% of population being males. In total 264(28.8%) patients were found to be seropositive. Residency in Delhi and non-smoking status conferred a higher risk for seropositivity. The adjusted odds ratio for seropositivity with regards to no smoking and residence out of Delhi were .31{+/-}.09 (Odds ratio {+/-} S.E) and .65 {+/-} .1 (Odds ratio {+/-} S.E) respectively. No other factors like age, socio-economic status, contact history etc showed significant relationship with seropositivity. ConclusionThe seropositivity rate among hospitalized patients was found to increase with time (from 8.45% to 38%) over a period of 9 months. Residence in Delhi and non-smokers had higher risk for seropositivity on multivariate analysis.
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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.
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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.
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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.
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BackgroundThe epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies. MethodsWe performed a case-control study comparing cases diagnosed with CAM and those who had recovered from COVID-19 without developing mucormycosis (controls). Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Results352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases carried conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95%CI 1.1-11), use of systemic steroids (aOR 7.7,95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6,95% CI 1.2-2.2). Zinc therapy, probably due to its utility in immune function, was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM. ConclusionJudicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM.
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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.
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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
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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.
