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Acanthamoeba is a rare cause of granulomatous amoebic encephalitis (GAE) associated with high mortality. There have been few case reports of Acanthamoeba meningoencephalitis worldwide. Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory condition caused by abnormally active macrophages and cytotoxic T lymphocytes; its secondary form is due to infections or malignancies. However, HLH is rather an unknown complication of GAE. We describe an unusual and previously unreported case of Acanthamoeba meningoencephalitis in a young immunocompetent female culminating in secondary HLH.

Background BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection. Methods We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 – odds ratio) × 100%. Findings Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33–62; p

COVID-19 causes morbid pathological changes in different organs including lungs, kidneys, liver, etc., especially in those who succumb. Though clinical outcomes in those with comorbidities are known to be different from those without - not much is known about the differences at the histopathological level.To compare the morbid histopathological changes in COVID-19 patients between those who were immunocompromised (Gr 1), malignancy (Gr 2), or had cardiometabolic conditions (hypertension, diabetes, or coronary artery disease) (Gr 3).Post-mortem tissue sampling (MITS) was done from the lungs, kidney, heart, and liver using a biopsy gun within two hours of death. Routine (HE stain) and special stains (AFB, SM, PAS) were done besides immunohistochemistry.A total of 100 patients underwent MITS and data of 92 were included (immunocompromised: 27, maligancy:18, cardiometabolic conditions:71). In lung histopathology, capillary congestion was more in those with malignancy while others like diffuse alveolar damage, microthrombi, pneumocyte hyperplasia, etc were equally distributed. In liver histopathology, architecture distortion was significantly different in immunocompromised while steatosis, portal inflammation, Kupffer cell hypertrophy, and confluent necrosis were equally distributed. There was a trend towards higher acute tubular injury in those with cardiometabolic conditions as compared to the other groups. No significant histopathological difference in heart was discerned.Certain histopathological features are markedly different in different groups (Gr 1,2 and 3) of COVID-19 patients with fatal outcomes. This article is protected by copyright. All rights reserved.

Post COVID-19 sequelae are a constellation of symptoms often reported after recovering from COVID-19. There is a need to better understand the clinical spectrum and long-term course of this clinical entity. The aim of this study is to describe the clinical features and risk factors of post COVID-19 sequelae in the North Indian population. This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 and February 2021. Patients aged >18 years with laboratory-confirmed COVID-19 were recruited after at least two weeks of diagnosis, and details were captured. A total of 1234 patients were recruited and followed up for a median duration of 91 days (IQR: 45-181 days). Among them, 495 (40.1%) had persistent symptoms post-discharge or recovery. In 223 (18.1%) patients, the symptoms resolved within four weeks; 150 (12.1%) patients had symptoms till 12 weeks, and 122 (9.9%) patients had symptoms beyond 12 weeks of diagnosis/symptom-onset of COVID-19. Most common symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), insomnia (1.4%), mood disturbances (0.48%) and anxiety (0.6%). Patients who were hospitalized were more likely to report fatigue as a feature of long COVID. Hypothyroidism (OR: 4.13, 95% CI: 2.2-7.6, p-value < 0.001) and hypoxia (SpO2 ≤ 93%) (OR: 1.7, 95% CI: 1.1-2.4, p-value 0.012) were identified as risk factors for long COVID sequelae. In conclusion, long COVID symptoms were common (22%), and 9.9% had the post COVID-19 syndrome. Myalgias, fatigue and dyspnoea were common symptoms. Patients with hypothyroidism and hypoxia during acute illness were at higher risk of long COVID.

Background Though invasive pulmonary aspergillosis is a well known complication of COVID‐19 pneumonia, indolent forms of aspergillosis have been rarely described. Methods We prospectively collected the clinico‐radio‐microbiological data of 10 patients of subacute invasive pulmonary aspergillosis (SAIA), who presented to our hospital with recent history of COVID‐19 pneumonia along with cavitary lung disease, positive IgG (against Aspergillus) with or without positive respiratory samples for Aspergillus spp. Result The mean age of presentation of SAIA was 50.7 ± 11.8 years. All the patients had recently recovered from severe COVID‐19 illness with a mean duration of 29.2 ± 12 days from COVID‐19 positivity. Cough was the predominant symptom seen in 8/10 (80%) patients followed by haemoptysis. 7/10 (70%) patients were known diabetic. While serum galactomannan was positive in 5/9 patients (55.5%), fungal culture was positive in 2/7 patients (28.5%) and polymerase chain reaction (PCR) for Aspergillus was positive in three patients. Eight (80%) patients presented with a single cavitary lesion; pseudoaneurysm of pulmonary artery was seen in two patients and post‐COVID‐19 changes were seen in all patients. All patients were treated with voriconazole, out of which four (40%) patients died during the follow‐up period. Conclusion SAIA should be considered in the differential diagnosis of cavitating lung lesions in patients with recent history of COVID‐19 in the background of steroid use with or without pre‐existing diabetes.

Introduction The COVID-19 pandemic has been a major public health threat for the past three years. The RNA virus has been constantly evolving, changing the manifestations and progression of the disease. Some factors which impact the progression to severe COVID-19 or mortality include comorbidities such as diabetes mellitus, hypertension, and obesity. In this study, we followed a cohort of patients to evaluate the risk factors leading to severe manifestations and mortality from COVID-19. Methodology We conducted a prospective observational study of 589 COVID-19 patients to assess the risk factors associated with the severity and mortality of the disease. Results In our cohort, 83.5% were male, with a median age (p25, p75) of 39.71 (30-48) years. The most common comorbidities included diabetes mellitus (7.8%) and hypertension (7.9%). About 41.7% had an asymptomatic disease, and of the symptomatic, 45% were mild, 6% moderate, and 7% severe. The mortality rate was 4.1%. Risk factors for severity included breathlessness (p=0.02), leukocytosis (p=0.02), and deranged renal function (p=0.04). Risk factors for mortality included older age (p=0.04), anemia (p=0.02), and leukocytosis (p=0.02). Conclusions COVID-19 commonly leads to asymptomatic or mild illness. The major factors we found that were associated with severity include breathlessness at presentation, leukocytosis, and deranged renal functions. The factors associated with mortality include older age, anemia, and leukocytosis.

Myelopathy in central nervous system tuberculosis is notorious for poor outcomes, determined by the severity of inflammation and cord level involved. Acute-onset quadriplegia or paraplegia in these cases represents a neuro-emergency. We report a young female with disseminated tuberculosis who presented with acute onset flaccid quadriparesis with loss of bladder and bowel function. Imaging helped identify the extensive involvement of the neuraxis. We propose that, in addition to anti-tubercular therapy, high-dose corticosteroids such as pulse methylprednisolone may result in a meaningful improvement and show greater rapidity of response in cases of severe central nervous system inflammation such as arachnoiditis or myelopathy.

Background The emergence of drug resistant tuberculosis (TB), is a major menace to cast off TB worldwide. Line probe assay (GenoType MTBDRplus ver. 2) and Xpert® MTB/RIF assays are two rapid molecular TB detection/diagnostic tests. Objective To compare the performance of line probe assay (LPA) and Xpert® MTB/RIF assay for early diagnosis of rifampicin-resistant (RR) TB in acid-fast bacillus (AFB) smear-positive and negative sputum samples. Methods A total 576 presumptive multidrug-resistant TB (MDR-TB) patients were selected and subjected to AFB microscopy, Xpert® MTB/RIF assay and recent version of LPA (GenoType MTBDRplus assay ver.2) tests directly on sputum samples. Results were compared with phenotypic culture and drug susceptibility testing (DST). DNA sequencing was performed with rpoB gene for samples with discordant rifampicin susceptibility results. Results Among culture-positive samples, Xpert® MTB/RIF assay detected Mtb in 97.3% (364/374) of AFB smear-positive samples and 76.5% (13/17) among smear-negative samples, and the corresponding values for LPA test (valid results with TUB band) were 97.9% (366/374) and 58.8% (10/17) respectively. For detection of RR among Mtb positive molecular results, the sensitivity of Xpert® MTB/RIF assay and LPA (after resolving discordant phenotypic DST results with DNA sequencing) were found to be 96% and 99% respectively. Whereas, specificity of both test for detecting RR were found to be 99%. Conclusion We conclude that although Xpert® MTB/RIF assay is comparatively superior to LPA in detecting Mtb among AFB smear-negative pulmonary TB. However, both tests are equally efficient in early diagnosis of AFB smear-positive presumptive RR-TB patients.

A rapid surge in cases during the COVID-19 pandemic can overwhelm any healthcare system. It is imperative to triage patients who would require oxygen and ICU care, and predict mortality. Specific parameters at admission may help in identifying them.A prospective observational study was undertaken in a COVID-19 ward of a tertiary care center. All baseline clinical and laboratory data were captured. Patients were followed till death or discharge. Univariable and multivariable logistic regression was used to find predictors of the need for oxygen, need for ICU care, and mortality. Objective scoring systems were developed for the same using the predictors.The study included 209 patients. Disease severity was mild, moderate, and severe in 98 (46.9%), 74 (35.4%), and 37 (17.7%) patients, respectively. The neutrophil-to-lymphocyte ratio (NLR)4 was a common independent predictor of the need for oxygen (p0.001), need for ICU transfer (p=0.04), and mortality (p=0.06). Clinical risk scores were developed (10*c-reactive protein (CRP) + 14.8*NLR + 12*urea), (10*aspartate transaminase (AST) + 15.7*NLR + 14.28*CRP), (10*NLR + 10.1*creatinine) which, if ≥14.8, ≥25.7, ≥10.1 predicted need for oxygenation, need for ICU transfer and mortality with a sensitivity and specificity (81.6%, 70%), (73.3%, 75.7%), (61.1%, 75%), respectively. Conclusion: The NLR, CRP, urea, creatinine, and AST are independent predictors in identifying patients with poor outcomes. An objective scoring system can be used at the bedside for appropriate triaging of patients and utilization of resources.

The clinical profile and risk factors for mortality in dengue fever have evolved over the years. The all-cause mortality in admitted dengue patients is around 6%. We aimed to evaluate the recent change in trends of the clinical characteristics and risk factors for in-hospital mortality in adults with dengue fever. This is a retrospective study on adults with confirmed dengue fever admitted in a medical unit of a tertiary care center in North India. Medical records of confirmed dengue fever patients admitted between January 2011, and December 2016 were reviewed. Chi-squared tests with Bonferroni correction for multiple testing were used to identify risk factors for mortality. 232 records were included, of which 66.8% were males. The mean age was 31.6 ± 14 years. There were 17 deaths with an all-cause mortality rate of 7.3% with 76.5% being classified as severe dengue at admission. Among the 17 mortality cases, dyspnea (47%), tachypnea (86.7%), leucocytosis (58.8%), raised urea (80%), and elevated serum creatinine (52.9%) at presentation were significantly associated with mortality (p < 0.001). Shock at any time during the hospital stay (58.8%) was also found to be significantly associated with mortality (p < 0.001). We found that dyspnea, tachypnea, acute kidney injury, and leucocytosis at presentation was significantly associated with in-hospital mortality. Based on our results, we recommend aggressive management of patients with severe dengue and those with mild/moderate disease with the above risk factors.

Arsenic has widespread use in agriculture, in alternative medicine and in treatment of certain malignancies, therefore it is vital to timely recognize and treat arsenic toxicity in a suspected patient. Hemodialysis conventionally is thought to play only a supportive role in managing arsenic toxicity but it can be life-saving when chelation is not possible or available. A middle-aged female with a history of non-dialysis-dependent chronic kidney disease (CKD) was brought to the emergency with altered sensorium. On presentation, she was hemodynamically stable with pallor and exfoliating lesions on palms, hyperkeratotic lesions on soles and hyperpigmented macules on the trunk. Investigations revealed pancytopenia and deranged kidney function tests. In view of skin lesions, the toxicological analysis was sent which revealed high levels of Arsenic (594 and 2,553 mcg/L in blood and urine respectively). Thus, a diagnosis of metabolic encephalopathy with the underlying cause being uremic or/and arsenic intoxication was made. Considering renal failure, she was managed with thrice-weekly hemodialysis. Chelation was not possible due to unavailability of agents during lockdown in Coronavirus disease (COVID-19) pandemic. Following dialysis, there was a significant improvement in sensorium, skin lesions, and pancytopenia depicting the utility of hemodialysis in such cases. Thus, hemodialysis is an effective and perhaps underutilized modality in the treatment of arsenic intoxication with impaired renal function.

Background Line probe assay (LPA) is standard diagnostic tool to detect multidrug resistant tuberculosis. Noninterpretable (NI) results in LPA (complete missing or light wild-type 3 and 8 bands with no mutation band in rpoB gene region) poses a diagnostic challenge. Methods Sputum samples obtained between October 2016 and July 2017 at the Intermediate Reference Laboratory, All India Institute of Medical Sciences Hospital, New Delhi, India were screened. Smear-positive and smear-negative culturepositive specimens were subjected to LPA Genotype MTBDRplus Ver 2.0. Smear-negative with culture-negative and culture contamination were excluded. LPA NI samples were subjected to phenotypic drug susceptibility testing (pDST) using MGIT-960 and sequencing. Results A total of 1,614 sputum specimens were screened and 1,340 were included for the study (smear-positive [n=1,188] and smear-negative culture-positive [n=152]). LPA demonstrated 1,306 (97.5%) valid results with TUB (Mycobacterium tuberculosis) band, 24 (1.8%) NI, three (0.2%) valid results without TUB band, and seven (0.5%) invalid results. Among the NI results, 22 isolates (91.7%) were found to be rifampicin (RIF) resistant and two (8.3%) were RIF sensitive in the pDST. Sequencing revealed that rpoB mutations were noted in all 22 cases with RIF resistance, whereas the remaining two cases had wild-type strains. Of the 22 cases with rpoB mutations, the most frequent mutation was S531W (n=10, 45.5%), followed by S531F (n=6, 27.2%), L530P (n=2, 9.1%), A532V (n=2, 9.1%), and L533P (n=2, 9.1%). Conclusion The present study showed that the results of the Genotype MTBDRplus assay were NI in a small proportion of isolates. pDST and rpoB sequencing were useful in elucidating the cause and clinical meaning of the NI results.

Background and Aim There is a paucity of data on the clinical presentations and outcomes of Corona Virus Disease-19 (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. Methods Patients with known chronic liver disease who presented with superimposed COVID-19 (n = 28) between 22 April 2020 and 22 June 2020 were studied. Seventy-eight cirrhotic patients without COVID-19 were included as historical controls for comparison. Results A total of 28 COVID-19 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 with 23.1% (18/78) in the historical controls (p = 0.077). All COVID-19 patients with ACLF (9/9) died compared with 53.3% (16/30) in ACLF of historical controls (p = 0.015). Mortality rate was higher in COVID-19 patients with compensated cirrhosis and AD as compared with 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. Conclusion COVID-19 is associated with poor outcomes in patients with cirrhosis, with worst survival rates in ACLF. Mechanical ventilation is associated with a poor outcome.

Background: Early diagnosis and treatment of drug-resistant tuberculosis (TB) is crucial to halt the spread of drug resistance in the community. Aim: The aim of the study was to compare rapid diagnostic tests (GeneXpert and line probe assay, LPA) with conventional liquid culture for the diagnosis of drug-resistant TB and to assess the risk factors for it. Method: This cross-sectional study recruited 229 multidrug-resistant TB suspects who were sputum smear positive. They were evaluated by the rapid diagnostic tests and sensitivity, specificity, positive predictive value and negative predictive value were calculated for drug resistance detection as compared to liquid culture drug susceptibility testing. The risk factors for the development of drug resistance were also assessed and the P value of < 0.05 was considered significant. Results: In the final comparison, 193 samples were included. The sensitivity and specificity of GeneXpert for detection of drug resistance (rifampicin) was 100% (95% confidence interval, CI: 88.8–100%) and 99.4% (95% CI: 96.6–99.9%), respectively. Whereas sensitivity and specificity of LPA was 94.3% (95% CI: 80.8–99.3%) and 100% (95% CI: 97.7–100%), respectively. Only three discordant samples were observed. Defaulting to antitubercular therapy, contact with resistant TB, and disseminated disease were found to be significant risk factors for the development of drug-resistant TB with high statistical significance (P value < 0.05). Conclusion: Both rapid diagnostic tests have very high sensitivity and specificity for detection of drug resistance in sputum smear positive with the advantage of short turn-around time. Defaulting to antitubercular therapy, contact with resistant TB, and disseminated disease are significant risk factors for drug resistance.

Background Mutations in atpE gene or transcriptional repressor Rv0678 gene associated with inhibition of adenosine 5'-triphosphate synthase and upregulation of efflux pumps, respectively, may potentially lead to in vitro resistance to bedaquiline. This is the first study from India, which looks at mutations associated with this novel drug. Methods In 2019 (January to June), a total of 68 laboratory-confirmed pre-extensively drug-resistant tuberculosis (XDR-TB) (fluoroquinolone resistant [n = 52] and second-line injectables resistant [n = 12]) and 4 × DR-TB culture specimens were included. All specimens were evaluated for genetic analysis using predesigned primers of atpE and Rv0678 genes. Results Among the pre-XDR-TB isolates (n = 64), there were no mutations found in either atpE or Rv0678. However, among the XDR-TB isolates (n = 4), one specimen (25%) was found to be associated with a mutation in atpE gene at position 49, resulting in the amino acid leucine replaced by proline (L-49-P). No mutations were observed with the Rv0678 gene. Conclusion In this study, genetic analysis showed that only one-fourth XDR-TB isolates had a mutation in the atpE gene; there were no other mutations found in the Rv0678 gene. To the best of our knowledge, this novel mutation (L-49-P) in atpE gene is being reported for the first time in northern India.

Use of systemic corticosteroids is well-established in COVID-19 patients with hypoxia; however, there is scant data on its role in patients with mild disease and prolonged symptoms as a measure to prevent disease progression. The aim of this study is to evaluate the role of systemic corticosteroids in preventing hypoxia (SpO2 ≤ 93% on room-air) among mild COVID-19 patients. An observational study was conducted among symptomatic COVID-19 patients taking oral corticosteroids and attending institute teleconsultation facility between 10th-30th June 2021. Patients who were already on corticosteroids for other indication or required oxygen supplementation before or within 24-hours of initiation of corticosteroids were excluded. A total of 140 consecutive symptomatic COVID-19 patients were included. Higher baseline C-reactive protein (OR: 1.03, 95% CI: 1.02-1.06, p < 0.001) and early systemic corticosteroid (within 7 days) initiation (OR: 6.5, 95% CI: 2.1-20.1, p = 0.001) were independent risk factors for developing hypoxia (SpO2 ≤ 93%). Progression to hypoxia was significantly higher in patients who received corticosteroids before day 7 of illness (36.7%, 95% CI, 23.4-51.7%) compared to ≥ 7 of illness (14.3%, 95% CI, 7.8-23.2%) for persistent fever. Systemic corticosteroids within 7 days from symptom-onset were harmful and increased the risk of progression to hypoxia, whereas it may decrease the risk of progression when administered on or beyond 7 days in patients with mild COVID-19 and persistent symptoms. A well-designed randomised controlled trial is required to validate the findings.

Objective This study was conducted to develop and validate a comprehensive questionnaire to assess bullying, discrimination, and harassment in healthcare settings. Methodology A mixed-method study design was used to develop and validate the questionnaire. In phase I, qualitative approaches were used for the development, which included literature search, focus group discussions (FGDs), following which the construct was developed. In phase II, face validity and construct validity were established using quantitative approaches. Results The final questionnaire consists of 25 items divided into five sections addressing the burden, impact, reasons for underreporting, risk factors, and mitigation strategies. The questionnaire has very good consistency with a Cronbach's alpha score of 0.86. Conclusion This is a comprehensive tool with appropriate psychometric properties with potential use for evaluating the problem of interpersonal discord in the form of bullying, harassment, and discrimination in a healthcare setting.

Background The 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. Methods We performed a case-control study comparing cases diagnosed with CAM and taking controls as recovered COVID 19 patients who did not develop mucormycosis. Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Multivariate regression analysis was used to identify the independent predictors. Results A total of 352 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 of 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 had 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 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. Conclusion Judicious 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.

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.

BackgroundLong 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.AimTo describe the clinical details and risk factors of post-COVID sequelae in the North Indian population.MethodThis 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.ResultsOf 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.ConclusionMost 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.

IntroductionThe 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.MethodsA retrospective cohort study was conducted in a tertiary referral centre where records of all adult COVID-19 patients (≥18 years) requiring HFNC support were between September and December 2020 were analysed. HFNC support was adjusted to target SpO2 ≥90% and respiratory rate ≤30 per min. The clinical, demographic, laboratory, and treatment details of these patients were retrieved from the medical records and entered in pre-designed 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.ResultsThirty-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).ConclusionsOur 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.

BackgroundSeroprevalence helps us to estimate the exact prevalence of a disease in a population. Although the world has been battling this pandemic for more than a year now, we still do not know about the burden of this disease in people living with HIV/AIDS (PLHA). Seroprevalence data in this population subset is scarce in most parts of the world, including India. The current study aimed to estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody among PLHA.AimTo determine the seroprevalence of SARS-CoV-2 antibodies in PLHA.MethodThis was a cross-sectional study conducted at a tertiary care hospital in North India. We 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.ResultsA total of 164 patients were recruited in the study with a mean age (±SD) of 41.2 (±15.4) years, of which 55% were male. Positive serology against SARS CoV-2 was detected in 14% patients (95% CI: 9.1-20.3%).ConclusionThe seroprevalence of COVID-19 infection in PLHA was lower than the general population in the same region, which ranged from 23.48% to 28.3% around the study period.

Hydroxychloroquine (HCQ) had generated considerable interest for coronavirus disease 2019 (COVID-19) prophylaxis. We conducted a prospective observational study at a tertiary care hospital in India, with dedicated COVID-19 care facilities.Primary objective was incidence of adverse effects, secondary objective being efficacy in preventing COVID-19.Healthcare workers were recruited and grouped based on voluntary HCQ prophylaxis as per national guidelines. Side effects in HCQ group were graded in accordance with national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 5.0. At 3-7-week follow-up, groups were compared for COVID-19 exposure, symptoms development and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR results.Among 358 participants recruited, 216 (60.3%) were males and mean age was 31.2 ± 6.6 years. Chemoprophylaxis was initiated by 258 (72%) participants. After loading dose, 7 (2.7%) reported grade 2 and 1 (0.4%) grade 3 adverse effects. Discontinuation of HCQ due to side effects was reported in 11 (4.3%) participants. Electrocardiogram was done by 50 (19.4%) participants on HCQ; no abnormalities were noted. A total of 106 (41%) among those taking and 63 (63%) among those not taking HCQ were tested for SARS-CoV-2 due to influenza-like illness or significant exposure. Among all participants, 25 (6.9%, 95% confidence interval [CI] 4.3-9.6) developed COVID-19 during the study period. In the group taking HCQ, 10 (3.9%) tested positive compared to 15 (15%) in the group not taking HCQ (HCQ is safe at the recommended dose for pre-exposure prophylaxis of COVID-19.

A 54-year-old man presented with a 1-month history of generalised weakness and a 2-day history of altered sensorium with poor response to verbal commands and repetitive speech, along with headache and vomiting. Neurological examination did not reveal any focal motor, sensory, or cerebellar

Background The phenomenon of Drug Resistant Tuberculosis (DRTB) has been evolving aggressively and is posing great threat to tuberculosis control programs worldwide. But what really is fueling drug resistance in high disease burden countries apart from other well known risk factors, with this intent in mind the present study was developed and carried out to. The aim was to capture the presence of Fluoroquinolone (FQ) mono-resistance among drug-sensitive TB cases. Methods A total of 1280 sputum smear-positive patients were enrolled in the study and were subjected for Drug Susceptibility Testing (DST) using First-Line Drugs (FLD's; Rifampicin, Streptomycin, Isoniazid and Ethambutol) using liquid culture DST and Line Probe Assay. These samples were further subjected to second-line drugs DST (ofloxacin and kanamycin) and DNA sequencing to confirm FQ mono-resistance. Results The occurrence of FQ mono-resistance among FLD sensitive cases was found to be 3.2% (35/1099). Xpert MTB/RIF assay and rpoB gene sequencing were showed 100% concordance with FLD DST. A total of 35 FQ mono-resistant isolates were further sequenced for gyrA, gyrB and rrs genes. The gene sequencing was found to be in agreement with the DST results for 34 (3.1%) isolates with gyrA and gyrB genes. Conclusion Presence of FQ resistance among drug sensitive TB cases is a red flag sign. The findings of the present study suggest that, second-line DST should be routinely performed not only for drug-resistant cases but also for drug-sensitive cases so as to capture prevailing true drug resistance at an initial stage.

Lymph node tuberculosis is one of the most common forms of extrapulmonary tuberculosis worldwide. The study aimed to evaluate the role of positron emission tomography-computed tomography (PET-CT) in determining post-treatment response in lymph node tuberculosis. A PET-CT was done in all treatment naive tubercular lymphadenitis adults at baseline and after six months of therapy. The post-treatment clinical response was compared with the metabolic response on PET-CT. Of the 25 patients with tubercular lymphadenitis, 9/25 patients showed a complete metabolic response (CMR) at six months, while 16 patients had a partial metabolic response (PMR). All patients with CMR had a good clinical response. However, discordance between clinical and PET findings was noticed in those with PMR. The role of PET-CT in evaluating post-treatment response in patients with tubercular lymphadenitis needs further evaluation with a larger sample size.

Objectives To study whether a trained convolutional neural network (CNN) can be of assistance to radiologists in differentiating Coronavirus disease (COVID)–positive from COVID-negative patients using chest X-ray (CXR) through an ambispective clinical study. To identify subgroups of patients where artificial intelligence (AI) can be of particular value and analyse what imaging features may have contributed to the performance of AI by means of visualisation techniques. Methods CXR of 487 patients were classified into [4] categories—normal, classical COVID, indeterminate, and non-COVID by consensus opinion of 2 radiologists. CXR which were classified as “normal” and “indeterminate” were then subjected to analysis by AI, and final categorisation provided as guided by prediction of the network. Precision and recall of the radiologist alone and radiologist assisted by AI were calculated in comparison to reverse transcriptase-polymerase chain reaction (RT-PCR) as the gold standard. Attention maps of the CNN were analysed to understand regions in the CXR important to the AI algorithm in making a prediction. Results The precision of radiologists improved from 65.9 to 81.9% and recall improved from 17.5 to 71.75 when assistance with AI was provided. AI showed 92% accuracy in classifying “normal” CXR into COVID or non-COVID. Analysis of attention maps revealed attention on the cardiac shadow in these “normal” radiographs. Conclusion This study shows how deployment of an AI algorithm can complement a human expert in the determination of COVID status. Analysis of the detected features suggests possible subtle cardiac changes, laying ground for further investigative studies into possible cardiac changes. Key Points • Through an ambispective clinical study, we show how assistance with an AI algorithm can improve recall (sensitivity) and precision (positive predictive value) of radiologists in assessing CXR for possible COVID in comparison to RT-PCR. • We show that AI achieves the best results in images classified as “normal” by radiologists. We conjecture that possible subtle cardiac in the CXR, imperceptible to the human eye, may have contributed to this prediction. • The reported results may pave the way for a human computer collaboration whereby the expert with some help from the AI algorithm achieves higher accuracy in predicting COVID status on CXR than previously thought possible when considering either alone. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-020-07628-5.

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 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].

Covid-19 disease can involve any organ system leading to myriad manifestations and complications. Cardiovascular manifestations are being increasingly recognised with the improved understanding of the disease. Acute coronary syndrome, myocarditis, arrhythmias, cardiomyopathy; heart failure and thromboembolic disease have all been described. The elderly and those with prior cardiac diseases are at an increased risk of mortality. Overlapping symptomatology, ability of drugs to cause QTc interval (start of Q wave to the end of T wave) prolongation on electrocardiogram and arrhythmias, potential drug interactions, the need to recognise patients requiring urgent definitive management and provide necessary bedside interventions without increasing the risk of nosocomial spread have made the management challenging. In the background of a pandemic, non-Covid-19 cardiac patients are affected by delayed treatment and nosocomial exposure. Triaging using telemedicine and artificial intelligence along with utilization of bedside rapid diagnostic tests to detect Covid-19 could prove helpful in this aspect.

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.

Microbiological diagnosis of extra-pulmonary tuberculosis (EPTB) has been one of the most difficult aspects of tuberculosis (TB) management. Availability of better imaging and diagnostic modalities has led to an increase in the number of diagnosed cases. The current upsurge in multidrug-resistant tuberculosis warrants routine testing of EPTB samples for resistance at baseline with shorter turn-around time. A total of 369 EPTB specimens were subjected to Ziehl-Neelsen (ZN) stain, liquid culture (LC) with phenotypic drug susceptibility testing, MTBDRplus V.2 and MTBDRsl V.2. The molecular categorisation of resistant specimens was further reconfirmed with sequencing. The sensitivity and specificity of MTBDRplus V.2 to detect Mycobacterium tuberculosis (MTB) when compared to ZN stain was 97.9% and 89.2%, respectively while it was 73.4% and 83.8%, respectively when compared to LC. Similarly, for MTBDRsl V.2, the sensitivity and specificity for detection of MTB when compared with ZN was 95.6% and 91.9%, respectively and 75% and 89.2%, respectively when compared to LC. In smear-positive specimens, 94% (141/150) and 86% (129/150) valid results were observed in MTBDRplus V.2 and MTBDRsl V.2, respectively. The utilisation of both MTBDRplus V.2 and MTBDRsl V.2 for the diagnosis of smear-positive EPTB specimens would be useful in programmatic management of TB in high-burden settings.