Seroprevalence of anti-SARS-CoV-2 IgG antibodies in admitted patients at a tertiary referral centre in North India (preprint)

Background: Seroprevalence 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. Method In this cross-sectional study which was conducted 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 clinic-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. Results A total of 916 patients were recruited over 11 months with mean age(plus/minus SD) 39.79 plus/minus 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 plus/minus .09 (Odds ratio plus/minus S.E) and .65 plus/minus .1 (Odds ratio plus/minus S.E) respectively. No other factors like age, socio-economic status, contact history etc. showed significant relationship with seropositivity. Conclusion The 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.

Human to animal transmission of COVID-19: a two-way road

The current understanding of the epidemiology of COVID-19 in animals is limited. The susceptibility, route of infection and infectivity of animals is unknown. With the nations facing a critical shortage in manufacturing and import of diagnostic tests, the capacity for ecological surveys in animals is limited. It is probable that some animals may behave as asymptomatic carriers, super-spreaders, natural reservoirs, or may suffer from symptomatic disease. Isolation of such hosts could be fundamental in curtailing the spread of the disease. In conclusion, the bilateral transmission of COVID-19 between humans and animals poses significant risk and needs to be interrupted to limit the spread of this deadly pandemic.

ACE2 Expression in Lungs of Severe COVID-19 Infection: A Study on Minimally Invasive Post- mortem Tissue Samples (preprint)

Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COVID-19 (COrona VIrus Disease 2019). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-9 patients for other indications. IHC for CD61 and CD163 were performed for assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. Quantification of immunostaining, random sampling, and correlation analysis was used to substantiate the morphologic findings. Our results show that among a total of 44 COVID-19 post-mortem lung tissues and 15 lung biopsies in non-COVID-19 patients included, ACE2 protein expression was significantly higher in COVID-19 patients than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.

Novel Risk Factors for Coronavirus Disease-Associated Mucormycosis (CAM): A Case Control Study During the Outbreak in India (preprint)

Background: The epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. In this study, we aimed to analyse the risk factors for CAM, in addition to those established for mucormycosis prior to COVID-19 pandemic.Methods: We performed a case-control study comparing patients diagnosed with CAM with those who had recovered from COVID-19 without developing mucormycosis. Information on comorbidities, glycaemic control, and practices related to COVID-19 prevention and management was recorded.Findings: One hundred fifty-two cases of CAM 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 ± 9·1 days after the symptom onset of COVID-19. All, but one patient, carried either of the conventional risk factors: diabetes and steroid use. On multivariate regression analysis, risk factors associated with increased odds of CAM included presence of diabetes (aOR 3·5, 95%CI 1·1–11), poor glycaemic control (p<0.05 for blood glucose levels >200 mg/dL), use of systemic steroids (aOR 7·7,95% CI 2·4–24·7), prolonged use of cloth and surgical masks (vs N95 masks, aOR 17·5, 95% CI 4·6-66·7), and repeated nasopharyngeal swab testing (aOR 1·6,95% CI 1·2–2·2).Interpretation: CAM is strongly associated with diabetes, poor glycaemic control, and systemic steroid use. Novel risk factors identified in our study include prolonged use of cloth and surgical masks vis-a-vis N95 masks, and repeated nasopharyngeal swab testing. Oxygen therapy and need for hospitalization for COVID-19 did not affect the risk of CAM.Funding Information: This was an investigator-initiated non-funded study.Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: The study was approved by the Institute Ethics Committee, AIIMS, Delhi, India. [IECPG-353/28.05.21].

Novel risk factors for Coronavirus disease-associated mucormycosis (CAM): a case control study during the outbreak in India (preprint)

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.

Post COVID-19 sequelae: A prospective observational study from Northern India (preprint)

Background: Long COVID, or post-COVID-19 sequelae, is being seen in a growing number of patients reporting a constellation of symptoms, both pulmonary and extrapulmonary. Studies on COVID-19 recovered patients are scarce. Thus, there is a need to add granularity to our existing knowledge about the course and long-term effects of the infection. Aim: To describe the clinical details and risk factors of post-COVID sequelae in the North Indian population. Method: This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 to February 2021. Patients aged >18 years with a confirmed COVID-19 disease were recruited after at least two weeks of diagnosis and interviewed for any post-COVID-19 symptoms. Results: Of 1234 patients recruited, who were followed up for a median duration of 91 days (IQR: 45-181 days), 495 (40.11%) patients had symptoms. In 223 (18.1%) patients, the symptoms resolved within four weeks, 150 (12.1%) patients had symptoms till twelve weeks, and 122 (9.9%) patients had symptoms beyond twelve weeks of diagnosis of COVID-19. Most common long COVID-19 symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), disturbed sleep (1.4%), mood disturbances (0.48%) and anxiety (0.6%). The major determinants of developing post-COVID-19 symptoms in the patients were hypothyroidism and the severity of the disease. Conclusion: Most often, patients complain of myalgias, fatigue, dyspnoea, cough and disturbed sleep. Patients who are hypothyroid or have recovered from moderate to severe COVID-19 are at higher risk of developing post-COVID sequelae. Therefore, a multidisciplinary approach is required to diagnose and manage COVID-19 recovered patients.

Use of HFNC in COVID-19 patients in non-ICU setting: Experience from a tertiary referral centre of north India and a systematic review of literature (preprint)

Introduction The rapid surge of cases and insufficient numbers of intensive care unit (ICU) beds have forced hospitals to utilise their general wards for administration of non-invasive respiratory support including HFNC(High Flow Nasal Cannula) in severe COVID-19. However, there is a dearth of data on the success of such advanced levels of care outside the ICU setting. Therefore, we conducted an observational study at our centre, and systematically reviewed the literature, to assess the success of HFNC in managing severe COVID-19 cases outside the ICU. Methods A retrospective cohort study was conducted in a tertiary referral centre where records of all adult COVID-19 patients (over 18 years) requiring HFNC support were between September and December 2020 were analysed. HFNC support was adjusted to target SpO2 over 90% and respiratory rate less than 30 per min. The clinical, demographic, laboratory, and treatment details of these patients were retrieved from the medical records and entered in predesigned proforma. Outcome parameters included duration of oxygen during hospital stay, duration of HFNC therapy, length of hospital stay and death or discharge. HFNC success was denoted when a patient did not require escalation of therapy to NIV or invasive mechanical ventilation, or shifting to the ICU, and was eventually discharged from the hospital without oxygen therapy; otherwise, the outcome was denoted as HFNC failure. Systematic review was also performed on the available literature on the experience with HFNC in COVID-19 patients outside of ICU settings using the MEDLINE, Web of Science and Embase databases. Statistical analyses were performed with the use of STATA software, version 12, OpenMeta[Analyst], and visualization of the risk of bias plot using robvis. Results Thirty-one patients receiving HFNC in the ward setting, had a median age of 62 (50 - 69) years including 24 (77%) males. Twenty-one (68%) patients successfully tolerated HFNC and were subsequently discharged from the wards, while 10 (32%) patients had to be shifted to ICU for non-invasive or invasive ventilation, implying HFNC failure. Patients with HFNC failure had higher median D-dimer values at baseline (2.2 mcg/ml vs 0.6 mcg/ml, p=0.001) and lower initial SpO2 on room air at admission (70% vs 80%, p=0.026) as compared to those in whom HFNC was successful .A cut-off value of 1.7 mg/L carried a high specificity (90.5%) and moderate sensitivity (80%) for the occurrence of HFNC failure. Radiographic severity scoring as per the BRIXIA score was comparable in both the groups(11 vs 10.5 out of 18, p=0.78 ). After screening 98 articles, total of seven studies were included for synthesis in the systematic review with a total of 820 patients, with mean age of the studies ranging from 44 to 83 years and including 62% males. After excluding 2 studies from the analysis, the pooled rates of HFNC failure were 36.3% (95% CI 31.1% - 41.5%) with no significant heterogeneity (I2 =0%, p=0.55). Conclusions Our study demonstrated successful outcomes with use of HFNC in an outside of ICU setting among two-thirds of patients with severe COVID-19 pneumonia. Lower room air SpO2 and higher D-dimer levels at presentation were associated with failure of HFNC therapy leading to ICU transfer for endotracheal intubation or death. Also, the results from the systematic review demonstrated similar rates of successful outcomes concluding that HFNC is a viable option with failure rates similar to those of ICU settings in such patients.

Seroprevalence of COVID-19 in HIV Population (preprint)

Background: seroprevalence helps us to estimate the exact prevalence of a disease in a population. More than a year since the identification of the disease, it is still not known the exact burden of the disease in the PLHA group. Seroprevalence data in this subset of the population is scarce in most part of the world, including India. The current study aimed to estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody among people living with HIV/AIDS. Aim: To determine the seroprevalence of SARS-CoV-2 antibodies in PLHA (People living with HIV/AIDS). Design: This was an observational prospective cohort study. Method: This cross-sectional study, conducted at a tertiary care hospital in North India, recruited HIV positive patients following at the ART centre of the institute. Anti-SARS-CoV-2 IgG antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the chemiluminescent immunoassay method. Results: A total of 164 patients were recruited in the study with mean age (+SD) of 41.2 (+15.4) years and 55% male population. Positive serology against SARS CoV-2 was detected in 14% patients (95% C 9.1-20.3%). Conclusion: The seroprevalence of COVID-19 disease in PLHA was found to be lower than the general population.

Clinical Characteristics And Outcomes of 16 Cases With COVID19 and Mucormycosis: Experience From A Tertiary Care Center In India and Review of Literature (preprint)

Background-The sharp uptick in the cases of mucormycosis in the background of the COVID19 pandemic is a cause of concern and the reasons and it’s impact remains to be seen. We studied the clinical characteristics in patients with mucormycosis and COVID19 co-infection and performed a literature review.Methods-This retrospective study was conducted at tertiary centre in India. All patients admitted with COVID19 and mucormycosis were included, clinical details were obtained from hospital records. We did review of literatures using the terms “SARS-CoV2” OR “COVID19” AND “Mucormycosis” AND “co-infection” on Pubmed published before February 20, 2021.Results-Sixteen cases (M:F–13:3), mean age 46·5 years (24-75years), were included. Fourteen had known risk factors for mucormycosis, the most common being diabetes mellitus. Most patients (n=14) were symptomatic with mucormycosis before diagnosis of COVID19. There was delay in surgery by 22.5 days (IQR–>17.75–29.5), pending SARS-CoV-2 RT-PCR negativity. There were six deaths in this cohort, unrelated to the COVID19 severity. The literature review revealed eleven case reports on co-infection. Patients who had developed mucormycosis were found to have history of mechanical ventilation.Conclusion-The apparent increase in the incidence of mucormycosis may be due to decompensation of underlying comorbidities (decreased access to healthcare), and increased use of immunosuppressants in COVID19. Patients with co-infection were noted to have poorer outcomes. 

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.

Clinico-pathological features in fatal Covid-19 Infection: A Preliminary Experience of a Tertiary Care Centre in North India using Post-Mortem Minimally Invasive Tissue Biopsies (preprint)

Background: The Covid-19 pandemic began in China in December 2019. India is the second most affected country, as of November 2020 with more than a 8.5million cases. Covid-19 infection primarily involves the lung with the severity of illness varying from influenza-like illness to acute respiratory distress syndrome. Other organs have also found to be variably affected. Studies evaluating the histopathological changes of Covid-19 are critical in providing a better understanding of the disease pathophysiology and guiding treatment. Minimally invasive biopsy techniques (MITS/B) provide an easy and suitable alternative to complete autopsies. In this prospective single-center study we present the histopathological examination of 37 patients who died with complications of Covid-19. Methods: This was an observational study conducted in the Intensive Care Unit of JPN Trauma Centre AIIMS. A total of 37 patients who died of Covid-19 were enrolled in the study. Post-mortem percutaneous biopsies were taken with the help of surface landmarking/ultrasonography guidance from lung, heart, liver, and kidneys; after obtaining ethical consent. The biopsy samples were then stained with haematoxylin and eosin stain. Immunohistochemistry (IHC) was performed using CD61 and CD163 in all lung cores. SARS-CoV-2 virus was detected using IHC with primary antibodies in selected samples. Details regarding demographics, clinical parameters, hospital course, treatment details, and laboratory investigations were also collected for clinical correlation. Results: A total of 37 patients underwent post-mortem minimally invasive tissue sampling. Mean age of the patients was 48.7years and 59.5% of them were males. Respiratory failure was the most common complication seen in 97.3%. Lung histopathology showed acute lung injury and diffuse alveolar damage in 78% of patients. Associated bronchopneumonia was seen in 37.5% of patients and scattered microthrombi were visualized in 21% of patients. Immunostaining with CD61 and CD163 highlighted megakaryocytes and increased macrophages in all samples. Immunopositivity for SARS-CoV-2 was observed in Type II pneumocytes. Acute tubular injury with epithelial vacuolization was seen in 46% of the renal biopsies but none of them showed evidence of microvascular thrombosis. 71% of the liver tissue cores showed evidence of Kupfer cell hyperplasia. 27.5% had evidence of submassive hepatic necrosis and 14% had features of acute on chronic liver failure. All the heart biopsies showed non-specific features such as hypertrophy with nucleomegaly with no evidence of myocardial necrosis in any of the samples. Conclusions The most common finding in this cohort is the diffuse alveolar damage with demonstration of SARS-CoV-2 protein in the acute phase of DAD. Microvascular thrombi were rarely identified in the lung, liver and kidney. Substantial hepatocyte necrosis, hepatocyte degeneration, Kupffer cell hypertrophy, micro, and macrovesicular steatosis unrelated to microvascular thrombi suggests that liver might be a primary target of Covid-19. This study highlights the importance of MITS/B in better understanding the pathological changes associated with Covid-19.

Efficacy of Famotidine for COVID-19: A Systematic Review and Meta-analysis (preprint)

Background: Coronavirus Disease 2019 (COVID-19) pandemic continues unabated in many parts of the world. In the absence of any definite antiviral therapy except some benefit of remdesivir, there is an ongoing search for effective therapy. Famotidine has been shown to reduce mortality in hospitalized patients in a few studies. We conducted a systematic review on the use of famotidine in COVID-19. Methods: We searched the databases Medline, Embase, Cochrane CENTRAL and Medrxiv. Title/abstract screening, full text screening and data abstraction were carried out in by two reviewers. Case series, cohort studies and randomized trials were included. Results: Five studies were eligible for inclusion: all were retrospective cohort or case series. Low quality evidence suggests a likely clinical benefit for the use of famotidine in decreasing mortality in hospitalized patients with moderate to severe COVID-19. A meta-analysis of two cohort studies showed a statistically significant decrease in the composite outcome for death and intubation with famotidine (HR 0.44, 95% CI 0.27 to 0.73). Conclusion: Further evidence from RCTs is required for famotidine to treat COVID 19.

Seroprevalence of anti-SARS-CoV-2 IgG antibody in hospitalized patients in a tertiary referral center in North India (preprint)

Background: Seroprevalence of IgG antibodies against SARS-CoV-2 is an important tool to estimate the true extent of infection in a population. However, seroprevalence studies have been scarce in South East Asia including India, which, as of now, carries the third largest burden of confirmed cases in the world. The present study aimed to estimate the seroprevalence of the anti-SARS-CoV-2 IgG antibody among hospitalized patients at one of the largest government hospital in India. Method: This cross-sectional study, conducted at a tertiary care hospital in North India, recruited consecutive patients who were negative for SARS-CoV-2 by RT-PCR or CB-NAAT. Anti-SARS-CoV-2 IgG antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum samples by the ELISA method. Results: A total of 212 hospitalized patients were recruited in the study with mean age (+/-SD) of 41.2 (+/-15.4) years and 55% male population. Positive serology against SARS CoV-2 was detected in 19.8% patients(95% CI 14.7-25.8). Residency in Delhi conferred a higher frequency of seropositivity 26.5% (95% CI 19.3-34.7) as compared to that of other states 8% (95% CI 3.0-16.4) with p-value 0.001. No particular age groups or socio-economic strata showed a higher proportion of seropositivity. Conclusion: Around, one-fifth of hospitalized patients, who were not diagnosed with COVID-19 before, demonstrated seropositivity against SARS-CoV-2. While there was no significant difference in the different age groups and socio-economic classes; residence in Delhi was associated with increased risk (relative risk of 3.62, 95% CI 1.59-8.21) Key Words: SARS-CoV-2 IgG Antibody, Seroprevalence, Hospitalized patient, COVID-19

Poor Outcomes in Patients with Cirrhosis and COVID-19 (preprint)

Background and AimThere is a paucity of data on the clinical presentations and outcomes of Coronavirus disease 2019(COVID-19) in patients with underlying liver disease. We aimed to summarize the presentations and outcomes of COVID-19 positive patients and compare with historical controls.MethodsPatients with known chronic liver disease who presented with superimposed COVID- 19(n=28) between 22nd April and 22nd June 2020 were studied. Seventy-eight cirrhotic patients from historical controls were taken as comparison group.ResultsA total of 28 COVID patients- two without cirrhosis, one with compensated cirrhosis, sixteen with acute decompensation (AD), and nine with acute-on-chronic liver failure(ACLF) were included. The etiology of cirrhosis was alcohol(n=9), non-alcoholic fatty liver disease(n=2), viral(n=5), autoimmune hepatitis(n=4), and cryptogenic cirrhosis(n=6). The clinical presentations included complications of cirrhosis in 12(46.2%), respiratory symptoms in 3(11.5%) and combined complications of cirrhosis and respiratory symptoms in 11(42.3%) patients. The median hospital stay was 8(7-12) days. The mortality rate in COVID-19 patients was 42.3%(11/26), as compared to 23.1%(18/78) in the historical controls(p=0.077). All COVID-19 patients with ACLF(9/9) died compared to 53.3%(16/30) in ACLF of historical controls(p=0.015). Mortality rate was higher in COVID patients with compensated cirrhosis and AD as compared to historical controls 2/17(11.8%) vs 2/48(4.2%), though not statistically significant (p=0.278). Requirement of mechanical ventilation independently predicted mortality (hazard ratio, 13.68). Both non-cirrhotic patients presented with respiratory symptoms and recovered uneventfully.ConclusionCOVID-19 is associated with poor outcomes in patients with cirrhosis, with worst survival rates in ACLF. Mechanical ventilation is associated with a poor outcome.

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.

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

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 (preprint)

Objectives- Ongoing 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. Design - Retrospective (observational ) study. Setting - COVID 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. Participants - Patients 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. Methods - Data 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 measures - Final outcome was noted in terms of course of the disease, patients discharged, still admitted (at time of conclusion of study) or death. Results -Out of 231 cases included, majority were males(78.3%) with a mean age of 39.8 years. Comorbidities were present in 21.2% of patients, diabetes mellitus and hypertension being most common. The most common symptoms were dry cough(81, 35%), fever(64, 27.7%), sore throat(36, 15.6%), and dyspnoea(24, 10.4%); asymptomatic infection was noted in 108(46.8%) patients. Presence of comorbidities was an independent predictor of symptomatic disease (OR-2.66; 95% CI 1.8 to 6.53, p= 0.03). None of the patients progressed to moderate to severe COVID-19. There were no deaths in this cohort. Conclusions - Patients 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 registration - Not applicable