Correlation of severity & clinical outcomes of COVID-19 with virus variants: A prospective, multicentre hospital network study.

BACKGROUND OBJECTIVES: The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants. METHODS: A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription-PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants. RESULTS: Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination. INTERPRETATION CONCLUSIONS: The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant.

Letter in Response to "Melioidosis in a Tertiary Care Center from South India: A 5-year Experience.

How to cite this article: Behera B, Mohanty S, Mishra B, Mohapatra PR. Letter in Response to "Melioidosis in a Tertiary Care Center from South India: A 5-year Experience. Indian J Crit Care Med 2023;27(5):368-369.

Spectrum of Bacterial Pathogens in Critical COVID-19 Patients Admitted in Intensive Care Units of a Tertiary Care Hospital During the First and Second Wave of the Pandemic.

OBJECTIVE: This study intends to compare the clinical characteristics and the prevalence and spectrum of bacterial pathogens in COVID-19 patients admitted to ICU during the first and second waves at a tertiary care, teaching and referral hospital of eastern India. METHOD: This is a hospital-based retrospective study which analysed demographic details, clinical profile and bacterial culture results of severe and critically ill COVID-19 patients admitted in intensive care units (ICU) during April -Oct 2020 (1st wave) and April -July 2021 (2nd wave). RESULT: The patients admitted during the 2nd wave were comparatively older and had multiple comorbidities compared to the 1st wave. (23.8%) (45/189) and 50% (173/346) of the COVID-19 patients admitted to ICU developed bacterial infection during the 1st and 2nd wave respectively. Overall, there was predominance of multidrug resistant Gram negative bacilli in both the waves. There was increased isolation of intrinsic colistin resistant microorganisms. CONCLUSION: Multidrug resistant Gram negative bacterial infections, remain a dreaded complication in severe and critically ill hospitalised COVID-19 patients requiring ICU care and high usage of colistin spirals the emergence and spread of pathogens intrinsically resistant to colistin.

Intricacies in characterizing positivity in pooled sample testing for SARS-CoV-2.

The unprecedented demand for testing for the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has led to an acute shortage and limited availability of test reagents for which pooling of samples has been recommended in areas with low prevalence. Considering the possibility of dilution factor in pool testing, an attempt was made to find out possibility of any true positive samples in pools with late amplification. The study was conducted on samples received from various collection centers in different districts of Odisha as well as from patients attending the screening clinic or admitted in COVID ward of the hospital. Nasal/nasopharyngeal/throat swabs received in viral transport media in cold chain were subjected to Real-time polymerase chain reaction (RT-PCR) testing in a Biosafety Laboratory level-2 by including uniform volume of four units (samples) per pool. All confirmed and probable positive pools in screening assay were de-convoluted and individual samples tested for confirmatory assay. Inclusion of an additional criteria of probable positive pool (Ct value >35 with non-sigmoid amplification curve or showing a line of amplification towards the end of the cycle) yielded 39 (15.5%) more true positive samples out of a total of 251 positive samples that would otherwise have been missed if only the classical criteria of positive (Ct within 35 with proper sigmoid curve) had been considered. The study highlights the importance of considering any indication of late amplification in the RT-PCR test to label a pool as positive to avoid missing any true positive sample in the pool.

Clinical Profile and Risk Factors for Severe Disease in 402 Children Hospitalized with SARS-CoV-2 from India: Collaborative Indian Pediatric COVID Study Group.

INTRODUCTION: There is a lack of large multicentric studies in children with COVID-19 from developing countries. We aimed to describe the clinical profile and risk factors for severe disease in children hospitalized with COVID-19 from India. METHODS: In this multicentric retrospective study, we retrieved data related to demographic details, clinical features, including the severity of disease, laboratory investigations and outcome. RESULTS: We included 402 children with a median (IQR) age of 7 (2-11) years. Fever was the most common symptom, present in 38.2% of children. About 44% had underlying comorbidity. The majority were asymptomatic (144, 35.8%) or mildly symptomatic (219, 54.5%). There were 39 (9.7%) moderate-severe cases and 13 (3.2%) deaths. The laboratory abnormalities included lymphopenia 25.4%, thrombocytopenia 22.1%, transaminitis 26.4%, low total serum protein 34.7%, low serum albumin 37.9% and low alkaline phosphatase 40%. Out of those who were tested, raised inflammatory markers were ferritin 58.9% (56/95), c-reactive protein 33.3% (41/123), procalcitonin 53.5% (46/86) and interleukin-6 (IL-6) 76%. The presence of fever, rash, vomiting, underlying comorbidity, increased total leucocyte count, thrombocytopenia, high urea, low total serum protein and raised c-reactive protein was factors associated with moderate to severe disease. CONCLUSION: Fever was the commonest symptom. We identified additional laboratory abnormalities, namely lymphopenia, low total serum protein and albumin and low alkaline phosphatase. The majority of the children were asymptomatic or mildly symptomatic. We found high urea and low total serum protein as risk factors for moderate to severe disease for the first time.

Utility of endobronchial ultrasound guided trans-bronchial needle aspiration in diagnosis of melioidosis - case series and review of literature.

Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is routinely performed for diagnostic evaluation of mediastinal lymphadenopathy due to various etiologies with excellent sensitivity and specificity. Melioidosis can have atypical features like isolated mediastinal lymphadenopathy mimicking as tuberculosis or lymphoma. Differentiation of such atypical melioidosis presentation become difficult due to similar clinical, radiological and even similar EBUS lymph node characteristics. Role of EBUS TBNA in diagnosing melioidosis is under investigated and sparsely reported. We describe two cases of melioidosis diagnosed by point of care rapid lateral flow immunoassay antigen testing and culture of EBUS-TBNA samples from necrotic mediastinal lymph nodes.

Antimicrobial resistance in beta-haemolytic streptococci in India: A four-year study.

BACKGROUND & OBJECTIVES: The incidence and severity of invasive and non-invasive infections demonstrate variability over time. The emerging resistance of Group A streptococci (GAS) to commonly used antibiotics is of grave concern. This study was conducted to assess the antimicrobial resistance of beta-haemolytic streptococci (ßHS) in India and to ascertain the molecular mechanisms of resistance. METHODS: All isolates of ßHS from the Trauma Centre of All India Institute of Medical Sciences (AIIMS) (north India), and heavily populated area of old Delhi from 2010 to 2014 and Yashoda Hospital, Secunderabad (in south India, 2010-2012) and preserved isolates of ßHS at AIIMS (2005-2009) were included. Phenotypic confirmation was done using conventional methods and the Vitek 2. Antibiotic sensitivity testing was done by disc diffusion and E-test. Detection of resistance genes, erm(A), erm(B), mef(A), tet(M) and tet(O), was done by polymerase chain reaction (PCR). RESULTS: A total of 296 isolates of ßHS (240 from north and 21 from south India) were included in the study. Of the 296 ßHS, 220 (74%) were GAS, 52 (17.5%) were Group G streptococci and 11 (3.7%), 10 (3.3%) and three (1%) were Group B streptococci, Group C streptococci and Group F streptococci, respectively. A total of 102 (46%) and 174 (79%) isolates were resistant to tetracycline and erythromycin, respectively; a lower resistance to ciprofloxacin (21, 9.5%) was observed. A total of 42 (14%) and 30 (10%) isolates, respectively, were positive for tet(M) and erm(B) genes. Only 13 (5%) isolates were positive for mef(A). None of the isolates were positive for erm(A) and tet(O). There was discordance between the results of E-test and PCR for erythromycin and tetracycline. INTERPRETATION & CONCLUSIONS: A high level of resistance to erythromycin and tetracycline was seen in ßHS in India. Discordance between genotypic and phenotypic results was reported. Absence of erm(A) and tet(O) with high prevalence of tet(M) and erm(B) was observed.

In vitro Activity of Fosfomycin against Multidrug-Resistant Urinary and Nonurinary Gram-Negative Isolates.

BACKGROUND: The era of multidrug-resistant (MDR) Gram-negative bacilli (GNB) has renewed interest in fosfomycin. AIM: The present study evaluated the in vitro activity of fosfomycin against MDR urinary and nonurinary GNB isolates. MATERIALS AND METHODS: Fosfomycin susceptibility was carried out by agar dilution for a total of 279 (142 from urine and 137 from other samples) MDR-GNB. Disk diffusion was done for urinary isolates only. RESULTS: Urinary tract isolates had a high degree of susceptibility to fosfomycin (overall susceptibility, 90.8%), whereas only 42.9% of nonurinary isolates retained susceptibility to the drug. Percentage susceptibility rates for urinary and nonurinary isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. were 99%, 91.3%, 66%, 0% and 62%, 44.4%, 32%, 11%, respectively. CONCLUSION: Fosfomycin showed excellent in vitro activity for uropathogens. Large-scale evaluation of fosfomycin against MDR systemic isolates is required to evaluate its therapeutic efficacy.

Antibiotic susceptibilities, streptococcal pyrogenic exotoxin gene profiles among clinical isolates of group C or G Streptococcus dysgalactiae subsp. equisimilis & of group G S. anginosus group at a tertiary care centre.

BACKGROUND & OBJECTIVES: Group C and group G streptococci (together GCGS) are often regarded as commensal bacteria and their role in streptococcal disease burden is under-recognized. While reports of recovery of GCGS from normally sterile body sites are increasing, their resistance to macrolides, fluoroquinolone further warrants all invasive ß haemolytic streptococci to be identified to the species level and accurately tested for antimicrobial susceptibility. This study was aimed to determine the prevalence, clinical profile, antimicrobial susceptibility and streptococcal pyrogenic exotoxin gene profile (speA, speB, speC, speF, smeZ, speI, speM, speG, speH and ssa) of GCGS obtained over a period of two years at a tertiary care centre from north India. METHODS: The clinical samples were processed as per standard microbiological techniques. ß-haemolytic streptococci (BHS) were characterized and grouped. Antimicrobial susceptibility of GCGS was performed using disk diffusion method. All GCGS were characterized for the presence of streptococcal pyrogenic exotoxins (spe) and spe genes were amplified by PCR method. RESULTS: GCGS (23 GGS, 2GCS) comprised 16 per cent of ß haemolytic streptococci (25/142 ßHS, 16%) isolated over the study period. Of the 25 GCGS, 22 (88%) were recovered from pus, two (8%) from respiratory tract, whereas one isolate was recovered from blood of a fatal case of septicaemia. Of the total 23 GGS isolates, 18 (78%) were identified as Streptococcus dysgalactiae subsp equisimilis (SDSE, large-colony phenotype), five (21%) were Streptococcus anginosus group (SAG, small-colony phenotype). The two GCS were identified as SDSE. All GCGS isolates were susceptible to penicillin, vancomycin, and linezolid. Tetracycline resistance was noted in 50 per cent of SDSE isolates. The rates of macrolide and fluoroquinolone resistance in SDSE were low. Twelve of the 20 SDSE isolates were positive for one or more spe genes, with five of the SDSE isolates simultaneously carrying speA+ speB+ smeZ+ speF or speB+ smeZ+speF, speI+speM+speG+speH or, speI+spe M+speH or speA+ speB+ speC+ smeZ+ speF. One notable finding was the presence of spe B in four of the five isolates of the Streptococcus anginosus group. No isolate was positive for ssa. INTERPRETATION & CONCLUSIONS: Our study showed no association between GCGS isolates harbouring streptococcal pyrogenic exotoxins and disease severity. This might be attributed to the small sample size of spe-positive isolates.

Indian tick typhus presenting as Purpura fulminans.

Seriously ill patients presenting with purpura fulminans, sepsis and multi-organ failure often require extensive diagnostic workup for proper diagnosis and management. Host of common infections prevalent in the tropics, e.g. malaria, dengue; other septicemic infections e.g. meningococcemia, typhoid, leptospirosis, toxic shock syndrome, scarlet fever, viral exanthems like measles, infectious mononucleosis, collagen vascular diseases (Kawasaki disease, other vasculitis) diseases, and adverse drug reactions are often kept in mind, and the index of suspicion for rickettsial illness is quite low. We present a case of Indian tick typhus presenting with purpura fulminans (retiform purpura all over the body), sepsis and multiorgan failure without lymphadenopathy and eschar, successfully treated with doxycycline and discharged home. Hence, a high index clinical suspicion and prompt administration of a simple therapy has led to successful recovery of the patient.

Scrub typhus in pregnancy: A report of two cases.

Scrub typhus shows a high prevalence in South-East Asia. In pregnant females, it can cause both maternal and fetal adverse outcomes. We report a case series of two women with scrub typhus and their varied outcomes. A 25-year-old primigravida treated for scrub typhus at 23 weeks' gestation presented at 34 weeks with stage three fetal growth restriction (FGR). Caesarean delivery was performed. The neonate had biliary atresia. A 24-year-old primigravida at 31 weeks' gestation was referred from a local hospital due to scrub typhus induced multi-organ dysfunction. She had FGR stage 1 with oligohydramnios. Emergency caesarean delivery was performed in view of acute fetal bradycardia. There is an emerging need for research to reassess what is already known about scrub typhus in pregnancy and to develop techniques for its treatment inorder to achieve a positive maternal and neonatal outcome in these cases.

Predictors for multidrug-resistant organisms (MDROs) carriage in haemodialysis patients.

Introduction: Infections in haemodialysis (HD) patients are an important cause of morbidity, hospitalization, and mortality. Patients undergoing HD are more prone to develop bacterial infections by multidrug-resistant organisms (MDROs). Objectives: This study is aimed to detect MDROs colonization in HD patients and its associated risk factors and outcome. Methodology: A total of 62 nasal swabs and 124 rectal swabs were collected from 62 patients coming to the haemodialysis unit from of March to May 2021 and were further screened for MRSA, VRE and CRE. Results: Out of 62 patients, 22.59% showed the presence of methicillin-resistant staphylococcus aureus (MRSA) while VRE was present in four patients (4/62). CRE was found as 24.2% (15/62). Duration of dialysis was found as a significant risk factor-associated MRSA carriage, Whereas Charlson index and drug and medication were found as significant risk factor for VRE carriage. Discussion & Conclusion: HD patients are particularly vulnerable to life threatening infections. Therefore, continuous epidemiological surveillance for these MDROs, including genotypic analysis and implementation of adequate decolonization strategies, is crucial and will reduce the possibility of autoinfection as well as disrupt transmission of multi-resistant isolates to others.

Microbiological profile of long COVID and associated clinical and radiological findings: a prospective cross-sectional study.

OBJECTIVE: To study the frequency of microbiological etiology of respiratory infections in patients with long COVID and their associated clinical and radiological findings. METHODS: Nasopharyngeal swabs and sputum specimens were collected from 97 patients with respiratory illness stemming from long COVID. The specimens were assessed for their microbiological profile (bacteria and virus) and their association with the overall clinical and radiological picture. RESULTS: In total, 23 (24%) patients with long COVID had viral infection (n = 12), bacterial infection (n = 9), or coinfection (n = 2). Microorganisms were detected at significantly higher rates in hospitalized patients, patients with moderate COVID-19, and patients with asthma (P < .05). Tachycardia (65%) was the most common symptom at presentation. A statistically significant number of patients with long COVID who had viral infection presented with cough and myalgia; and a statistically significant number of patients with long COVID who had bacterial infection presented with productive coughing (P < .05). Post-COVID fibrotic changes were found in 61% of cohort patients (31/51). CONCLUSION: A decreasing trend of respiratory pathogens (enveloped viruses and bacteria) was found in long COVID. An analysis including a larger group of viral- or bacterial-infected patients with long COVID is needed to obtain high-level evidence on the presenting symptoms (cough, myalgia) and their association with the underlying comorbidities and severity.

Diagnosis of a recurred lesion in dermatophytosis patients after 2 weeks of antifungal therapy: A prospective observational study.

Few researchers believe that various risk factors may complicate the course of dermatophytosis and/or develop various dermatoses unrelated to fungal infection at the previous lesion site. However, there is a paucity of studies that analyzed the diagnosis of lesions that recurred at the treated site of dermatophytosis. Materials and Methods: A prospective observational study was conducted on 157 cases of dermatophytosis with positive fungal test results. A fixed dose of 100 mg of oral itraconazole once daily was administered to all patients for 2 weeks. At the end of 2 weeks, patients were assessed for clinical cure and recurrence. Recurred cases were assessed for mycological profile using a fungal test (potassium hydroxide mount and/or fungal culture) for identifying fungal infection. Results: Only eight (5.36%) patients showed clinical cure, and 141 (94.63%) patients developed recurrence after therapy. Of the 141 cases with recurrence, only 47 (33.33%) patients were positive for fungus. Eight (5.09%) patients were lost to follow-up. Frequently encountered risk factors in the study were topical steroid use, disease in family, associated atopic dermatitis and contact with pets. Conclusion: This is the first study that described the clinical diagnosis and mycological profile of the various lesions recurring at the previous tinea infection site in patients with dermatophytosis. Such patients presented not only with recurrent lesions of fungal infection but also developed various dermatoses unrelated to fungal infection at the sites of previous tinea infection. Various factors, which could have resulted in the observed changes, are reinfection by dermatophytes at the sites of previous tinea infection, inadequate antifungal therapy or antifungal resistance; or due to the effects of various topical steroid formulations used by the patients, such as anti-inflammatory or immunosuppressive effects or shift in immunity. Hence, diagnosis of the recurrent lesion at the site of previous dermatophytosis must be individualized and should be based on 1) duration of antifungal therapy received, 2) associated risk factors, 3) response to antifungal therapy, 4) evolution of the recurrent lesion, and/or 5) fungal tests.

Surveillance of ventilator associated pneumonia in a network of indian hospitals using modified definitions: a pilot study.

Background: Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in patients receiving mechanical ventilation in India. Surveillance of VAP is essential to implement data-based preventive measures. Implementation of ventilator-associated events (VAE) criteria for surveillance has major constraints for low resource settings, which can lead to significant underreporting. Surveillance of VAP using common protocols in a large network of hospitals would give meaningful estimates of the burden of VAP in low resource settings. This study leverages a previously established healthcare-associated infections (HAI) surveillance network to develop and test a modified VAP definition adjusted for Indian settings. Methods: In this observational pilot study, thirteen hospitals from the existing HAI surveillance network were selected for developing and testing a modified VAP definition between February 2021 and April 2023. The criteria used for diagnosing VAP were adapted from the CDC's Pediatric VAP definition and modified to cater to the needs of Indian hospitals. Designated nurses recorded each VAP event in a case report form (CRF) and also collected denominator data. The data was entered into an indigenously developed database for validation and analysis. At the time of data analysis, a questionnaire was sent to sites to get feedback on the performance of the modified VAP definitions. Findings: Out of 133,445 patient days and 40,533 ventilator days, 261 VAP events were recorded, with an overall VAP rate of 6.4 per 1000 ventilator days and a device utilization ratio (DUR) of 0.3. A total of 344 organisms were reported from the VAP events. Of these, Acinetobacter spp (29.6%, 102) was the most frequent, followed by Klebsiella spp (26.7%, 92). Isolates of Acinetobacter spp (98%) and Enterobacterales (85.5%) showed very high resistance against Carbapenem. Colistin resistance was observed in 6% of Enterobacterales and 3.2% of Acinetobacter spp. Interpretation: Data from this pilot study needs to validated in the larger Indian HAI surveillance network so that it can help in wider implementation of this protocol in order to assess its applicability p VAP across India. Funding: This work was supported by a grant received from the Indian Council of Medical Research (code I-1203).