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.

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 (preprint)

Background Due 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. Methods This 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. Results Completing 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. Conclusion With 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 context Evidence before this study The Government of India started vaccinating its citizens from the 16 th 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 study This 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 48·5% 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 evidence The 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’.

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

Background The 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. Methods This 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. Findings A 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. Interpretation This 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 context Evidence before this study The 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 study This 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 evidence This 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.

Post-COVID-19 respiratory management: expert panel report

This report is the first expert panel report on the management of post-COVID-19 patients from India. The report contains high risk groups, post-COVID-19 patient management at primary care level, general principles of medical management of post-COVID-19 in primary care settings, management of post-COVID-19 symptoms in primary care settings, recommendations for inclusion and exclusion into the Pulmonary Rehabilitation Programme, post-COVID-19 patient management at tertiary care level, post-COVID-19 complete assessment and management, and respiratory disease-specific conditions requiring expert opinion and further research.

Leveraging Healthcare Facility Network Simulations for Capacity Planning and Facility Location in a Pandemic (preprint)

The COVID-19 pandemic has placed severe demands on healthcare facilities across the world, and in several countries, makeshift COVID-19 centres have been operationalised to handle patient overflow. In developing countries such as India, the public healthcare system (PHS) is organised as a hierarchical network with patient flows from lower-tier primary health centres (PHC) to mid-tier community health centres (CHC) and further downstream to district hospitals (DH). A network-based modelling and simulation (M&S) approach would (a) quantify the extent to which existing PHC, CHC and DH facilities can effectively cope with the forecasted COVID-19 patient load, whilst continuing to offer non-COVID-19 related care functions such as childbirth care, surgeries and outpatient clinics; (b) inform decisions on capacity at makeshift COVID-19 Care Centres (CCC) to handle patient overflows from the PHS; (c) enable identifying the optimal location of such makeshift facilities. We apply the network-based M&S approach to an empirical study of a local PHS comprising ten PHCs, three CHCs, one DH and one makeshift CCC, and report operational outcomes for existing PHS capacity and estimate the required capacity for the CCC under a specific pandemic response strategy. We identify the optimal location of the CCC through the combined application of the network simulation with a version of the stochastic ruler algorithm customized for this problem. Our work contributes to the literature on network modelling using simulation and optimisation approaches. Although this paper concerns COVID-19 operations management and CCC capacity planning, the approach could be used more generally in a pandemic situation.

Ivermectin in mild and moderate COVID-19 (RIVET-COV): a randomized, placebo-controlled trial (preprint)

Introduction: Till date, no drug has shown definite benefit in non-severe COVID-19. Ivermectin is an antiparasitic drug which has in-vitro efficacy in reducing coronavirus-2 (SARS-CoV-2) load in severe disease. Objectives: To determine if a single oral administration of Ivermectin to patients with mild and moderate COVID-19 is effective in converting SARS-CoV-2 RT-PCR to negative result and in reducing viral load.Methods: In this double-blind trial, patients were randomized to elixir formulation of Ivermectin in 24 mg, 12 mg or placebo in 1:1:1 ratio. The co-primary outcomes were conversion of RT-PCR to negative result and the decline of viral load at day 5 of enrolment and were assessed in patients with positive RT-PCR at enrolment (modified intention-to-treat population). Safety outcomes included total and serious adverse events and were assessed in all patients who received the trial drug (intention-to-treat population). Results: Among 157 patients randomized, 125 patients were included in mITT analysis. Forty patients each were assigned to Ivermectin 24 mg and 12 mg, and 45 patients to placebo. The RT-PCR negativity at day 5 was higher in the two Ivermectin arms but failed to attain statistical significance (Ivermectin 24 mg, 47.5%; 12 mg, 35.0%; and placebo, 31.1%; p= 0.30). The decline of viral load at day 5 was similar in the three arms. No serious adverse events were encountered.Conclusion: In patients with mild and moderate COVID-19, a single administration of Ivermectin elixir (either 24 mg or 12 mg) demonstrated a trend towards higher proportion of RT-PCR negativity at day 5 of enrolment. The protocol was registered in the Clinical Trial Registry – India (CTRI) vide ref No CTRI/2020/06/026001. 

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

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.

Chloroquine and Hydroxychloroquine for the treatment of COVID-19: A Systematic Review and Meta-analysis (preprint)

Background: There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. Objective: We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19. Methods: Two reviewers searched for published and pre-published relevant articles between December 2019 to 8th June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa scale. The quality of evidence was graded as per the GRADE approach. Results: We reviewed 12 observational and 3 randomized trials which included 10659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46] , time to fever resolution [mean difference -0.54 days (-1.19-011)] or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes. Conclusions: The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.