Long COVID following Omicron wave in Eastern India-A retrospective cohort study.

Long coronavirus disease (COVID) or postacute sequelae of coronavirus disease of 2019 (COVID-19) is widely reported but the data of long COVID after infection with the Omicron variant is limited. This study was conducted to estimate the incidence, characteristics of symptoms, and predictors of long COVID among COVID-19 patients diagnosed during the Omicron wave in Eastern India. The cohort of COVID-19 patients included were adults (≥18 years) diagnosed as severe acute respiratory syndrome coronavirus 2 positive with Reverse Transcription Polymerase Chain Reaction. After 28 days of diagnosis; participants were followed up with a telephonic interview to capture data on sociodemographic, clinical history, anthropometry, substance use, COVID-19 vaccination status, acute COVID-19 symptoms, and long COVID symptoms. The long COVID symptoms were self-reported by the participants. Logistic regression was used to determine the predictors of long COVID. The median follow-up of participants was 73 days (Interquartile range; 67-83). The final analysis had 524 participants' data; among them 8.2% (95% Confidence Interval [CI]: 6%-10.9%) self-reported long COVID symptoms. Fatigue (34.9%) was the most common reported symptom followed by cough (27.9%). In multivariable logistic regression only two predictors were statistically significant-number of acute COVID-19 symptoms ≥ five (Adjusted odds ratio (aOR) = 2.95, 95% CI: 1.30-6.71) and past history of COVID-19 (aOR = 2.66, 95% CI: 1.14-6.22). The proportion of self-reported long COVID is considerably low among COVID-19 patients diagnosed during the Omicron wave in Eastern India when compared with estimates during Delta wave in the same setting.

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.

High proportion of low cycle threshold value as an early indicator of COVID-19 surge.

Many countries in the world are experiencing a recent surge in COVID-19 cases. This is mainly attributed to the emergence of new SARS-CoV-2 variants. Genome sequencing is the only means to detect the evolving virus mutants and emerging variants. Cycle threshold values have an inverse relationship with viral load and lower Ct values are also found to be associated with increased infectivity. In this study, we propose to use Ct values as an early indicator for upcoming COVID-19 waves. A retrospective cross-sectional study was carried out to analyze the Ct values of positive samples reported during the first wave and second wave (April 2020-May 2021). Median Ct values of confirmatory genes were taken into consideration for comparison. Ct values below 25, >25-30, and >30 were categorized as high, moderate, and low viral load respectively. Our study found a significantly higher proportion of positive samples with a low Ct value (<25) across age groups and gender during the second wave of the COVID-19 pandemic. A higher proportion of positive samples with a low Ct value (high viral load) may act as an early indicator of an upcoming surge.

Clinical review of COVID-19 in children and adolescents with cancer: Experience from a tertiary care center in East India.

Children with underlying cancer are often immunocompromised. Data on severity of coronavirus disease 2019 (COVID-19) in children with cancer and its outcomes is emerging. Treatment protocols of specific cancers are decided based on the infrastructure, availability of supportive-care, and logistic issues of the locality. The purpose of the study was clinical analysis of COVID-19 in children and adolescents with cancer. The retrospective observational study was conducted at a tertiary healthcare-center in East India. Children and adolescents (aged 0-19 years) with cancer and under treatment with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) confirmed COVID-19 between 5-July-2020 and 5-December-2020 were studied. Median age of the 68 identified patients was six years. Acute leukemia was the most common (66%) diagnosis. COVID-19 was asymptomatic/mildly symptomatic in 91% and moderate to severe in only 9% of patients. Fever (87%) was the commonest symptom, followed-by cough/coryza (75%). Three patients with acute myeloid leukemia (AML) and severe/critical COVID-19 and associated neutropenic sepsis were required transfer to the intensive-care-unit (ICU) for management. Three (4.4%) patients succumbed with COVID-19. Delay in treatment was observed in 63.2% of patients, and the median duration of delay was 28 days after acquiring COVID-19. Median time to attain negative COVID-19 RT-PCR was 16 days, and eight patients were repeat positives. While pediatric and adolescent cancer patients on active treatment may have a higher risk of mortality from severe COVID-19 than their healthy counterparts, the risk may be much lower than deemed. It is essential to continue cancer therapy in these children. Delay in treatment remains a concern.

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.

Tuberculous splenic abscess in the immunocompetent host: a report and review of literature.

Tubercular splenic abscess is rare, particularly in immunocompetent patients. Diagnostic difficulties usually arise in patients with tubercular splenic abscess because of its non-specific presentation. We report an elderly male who presented with cough and fever and had pulmonary infiltrates suspicious of tuberculosis. Bronchoalveolar lavage microbiology including XpertMTB/Rif assay was non-contributory. Contrast enhanced computed tomography scan of abdomen revealed multiple non-enhancing lesions in the spleen. Ultrasound guided splenic aspirate revealed pus that was positive for Mycobacterium tuberculosis in XpertMTB/Rif assay confirming the diagnosis of tuberculosis.

Inhibition of coxsackievirus infection in cardiomyocytes by small dsRNA targeting its cognate coxsackievirus adenovirus receptor.

Background & objectives: Coxsackievirus B (CVB), a member of human Enterovirus group, is the most common cause of viral myocarditis. Coxsackievirus adenovirus receptor (CAR) is identified as a key determinant for the entry of CVB in the target cells. Thus, blockade of receptor by RNA interference (RNAi) may inhibit the entry and pathogenesis of CVB in cardiac cells. The present study was aimed to determine the effect of CAR small dsRNA (siRNA) on coxsackieviral load and CAR expression in coxsackievirus-infected cardiomyocytes. Methods: Transfection efficiency in rat cardiomyocytes (H9c2) was determined by the fluorescent microscopy and flow cytometry. CAR siRNA dose was optimized based on cell viability and relative CAR messenger RNA (mRNA) expression. Cardiomyocytes were transfected with CAR siRNA followed by infection with 100 multiplicity of infection of CVB, which were harvested after 24, 48 and 72 h post-infection (p.i.). RNA was extracted for relative CAR mRNA expression. Cells were freeze-thawed thrice for estimating coxsackieviral load. Results: The efficiency of transfection was optimized to be >80 per cent and CAR siRNA dose of 60 pmol was standardized. The knockdown of CAR by siRNA decreased its expression twice the expression in normal cardiomyocytes after 24 h p.i. of CVB. The treatment with CAR siRNA resulted in significant two log reduction of CVB load in cardiomyocytes infected with CVB at 24 h p.i. and retained till 72 h p.i. Interpretation & conclusions: The inhibition of CAR by siRNA was found to be effective against CVB in cardiomyocytes. However, this treatment strategy has to be evaluated in vivo to develop a new treatment strategy for patients suffering with viral myocarditis.

Role of coxsackievirus and adenovirus receptor (CAR) expression and viral load of adenovirus and enterovirus in patients with dilated cardiomyopathy.

Enteroviruses (EVs) and adenoviruses (AdVs) are two important etiological agents of viral myocarditis and dilated cardiomyopathy (DCM). Both these viruses share a common receptor, the coxsackievirus and adenovirus receptor (CAR), for their infection. However, the role of viral load and CAR expression in disease severity has not yet been completely elucidated. The present study aimed to determine viral load of EV and AdV in DCM patients and correlate them with the level of CAR expression in these patients. Sixty-three DCM cases and 30 controls, each of whom died of heart disease other than DCM and non-cardiac disease respectively, were included. Viral load was determined by TaqMan real-time PCR using primers and probes specific for the AdV hexon gene and the 5'UTR region of EV. The CAR mRNA level was semi-quantitated by RT-PCR, and antigen expression was studied by immunohistochemistry. A significantly high AdV load (p < 0.05) and CAR expression (p < 0.05) were observed in DCM cases versus controls, whereas the EV load showed no significant difference. The data suggests a clinical threshold of 128 AdV copies/500 ng of DNA for DCM, with 66.7 % sensitivity and 65 % specificity. A positive correlation between AdV load and CAR expression (p < 0.001) was also observed in DCM cases. The high adenoviral load and increased CAR expression in DCM and their association with adverse disease outcome indicates role of both virus and receptor in disease pathogenesis. Thus, the need for targeting both the virus and the receptor for treatment of viral myocarditis and early DCM requires further confirmation with larger studies.

A case of systemic melioidosis: unravelling the etiology of chronic unexplained fever with multiple presentations.

Melioidosis, caused by the environmental saprophyte, Burkholderia pseudomallei, is an important public health problem in Southeast Asia and Northern Australia. It is being increasingly reported from other parts, including India, China, and North and South America expanding the endemic zone of the disease. We report a case of systemic melioidosis in a 58-year-old diabetic, occupationally-unexposed male patient, who presented with chronic fever, sepsis, pneumonia, pleural effusion and subcutaneous abscess, was undiagnosed for long, misidentified as Pseudomonas aeruginosa infection elsewhere, but was saved due to correct identification of the etiologic agent and timely institution of appropriate therapy at our institute. A strong clinical and microbiological suspicion for melioidosis should be considered in the differential diagnosis of acute pyrexia of unknown origin, acute respiratory distress syndrome and acute onset of sepsis, especially in the tropics.

Persistence of human parvovirus B19 in tissues from adult individuals: a comparison with serostatus and its clinical utility.

Human parvovirus B19 (PVB19) is linked to variety of diseases, including erythema infectiosum, transient aplastic crisis, fetal hydrops, cardiomyopathy and, recently, hepatitis and arthritis. Persistence of PVB19 in asymptomatic individuals has been reported in skin, synovium, myocardium and bone marrow. A higher level of PVB19 DNA has been observed in various tissues from cases of disease than in controls. Simultaneously, equal detection of PVB19 DNA has been shown in both cases and controls. Thus, it has become fundamental to study PVB19 DNA persistence in tissues that are unaffected by disease. This will help to better understand PVB19 DNA persistence in symptomatic and asymptomatic individuals and its possible pathogenic role in various diseases. A total of 70 adult autopsies were included and divided into seropositive (SP) and seronegative (SN) groups based on PVB19 IgG. Nested PCR for PVB19 DNA was carried out in myocardium, liver, kidney, and bone marrow. Of the 70 patients, 60% belonged to the SP group and 40% to the SN group. Seropositivity ranged from 50% in the 12 to 20 year old group to 66.7% in the 61 to 80 year old group. The viral genome was detected in 34.3% of myocardium, 20% of bone marrow, 10% of kidney and 8.6% of liver samples. There was no significant difference in the persistence rates between the SP and SN groups. The persistence of PVB19 DNA in various tissues ranged from 8.3% to 36% in the SP group and 10% to 30% in the SN group. The persistence of PVB19 DNA in all the tissues was low, and PVB19 serostatus had no influence on the persistence of PVB19 DNA.

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.

Molecular characterization of coxsackievirus A24 variants isolated from an outbreak of acute hemorrhagic conjunctivitis.

PURPOSE: Acute Hemorrhagic conjunctivitis (AHC) is associated with CVA24v. Recently there was a severe outbreak of conjunctivitis in months of July and August 2023 in India. This study emphasizes the identification of the distinct mutations in the CVA24v strains, which were isolated during the AHC outbreak and could have potentially played a role in the high transmission of AHC in India during the 2023 outbreak. METHODS: A total of 71 conjunctivitis patients aged 1-75 years comprising 47 males and 24 females who attended Ophthalmology department of a tertiary care hospital of easternIndia were studied.RNA was extracted from all conjunctival swab samples and converted into cDNA. Subsequently, the viral 5' UTR was amplified and the PCR positive samples were subjected to sequencing. The newly isolated viral 5' UTR sequences were aligned with other worldwide sequences using the Clustal W tool to conduct mutational analysis. A phylogenetic tree was built using the MEGA software for viral genotype identification. RESULTS: All of the current outbreak strains belonged to genotype IV of CVA24v. The present outbreak strains formed a distinct clade in the phylogenetic tree and were different from previously reported Indian strains. Two persistent mutations, specifically in domain IV (T213C) and domain V (C475T), were exclusively detected within the internal ribosome entry site (IRES) of the 5' UTR of the current strains causing the outbreak. These two alterations have previously been shown to impact the virulence of another enterovirus (CV B3), but they have not been described in CVA24v until now. CONCLUSION: Finding of the present study highlights the possibility and the significance of the aforementioned two mutations in enhancing the transmissibility of the newer CVA24v strains. Hence, these two distinct mutations should be investigated further for developing antiviral therapies to combat future AHC outbreaks associated with CVA24v.

Pathogenic Role of Human Rhinovirus Mono-Infection in Pediatric Lower Respiratory Tract Infection.

Background and objective Human rhinovirus (HRV) is one of the leading causes of pediatric respiratory tract infection with a prevalence rate of 30-50%, mostly affecting children below five years of age and causing a substantial amount of economic loss. In children, it can alone or as a co-infection, cause a wide range of symptoms from mild to life-threatening ones. With the above background, the current study was carried out to emphasize the role of HRV mono-infection in pediatric acute respiratory tract infections by correlating clinical and molecular laboratory findings. Methods This study was carried out in a tertiary care teaching hospital over a duration of four years (March 2019-October 2023). Children up to 14 years of age visiting the outpatient department or admitted to the ward with diagnoses of acute respiratory tract infections (ARTIs) were included. The clinical and laboratory data were retrieved and analyzed. A nasopharyngeal swab (NPS) or throat swab (TS) was collected and sent to the Microbiology laboratory maintaining the cold chain. Nucleic acid was extracted and subjected to multiplex real-time polymerase chain reaction (RT-PCR). Result Of the 245 samples tested for the respiratory viral pathogen, 52 samples tested positive for HRV, of which 27 had HRV mono-infection. The clinico-demographic details of these 27 patients were studied in detail. The majority of the cases (24/27; 88.8%) were less than five years of age. Fever and shortness of breath were the most consistent symptoms in all. Nineteen (19/27; 62.9%) HRV mono-infection cases had underlying co-morbidities, all requiring respiratory support. The HRV mono-infection cases either developed bronchiolitis, lower respiratory tract infection, or pneumonia. All mono-infection cases had cycle threshold value (Ct) < 25, while the Ct value of HRV was > 30 in co-infection with other viruses. Conclusion Mono-infection of HRV in under-five children with underlying comorbidities and a lesser Ct value indicates severe disease manifestation and should be dealt with more cautiously.

Rubella immunity among pregnant women and the burden of congenital rubella syndrome (CRS) in India, 2022.

BACKGROUND: India aims to eliminate rubella and congenital rubella syndrome (CRS) by 2023. We conducted serosurveys among pregnant women to monitor the trend of rubella immunity and estimate the CRS burden in India following a nationwide measles and rubella vaccination campaign. METHODS: We surveyed pregnant women at 13 sentinel sites across India from Aug to Oct 2022 to estimate seroprevalence of rubella IgG antibodies. Using age-specific seroprevalence data from serosurveys conducted during 2017/2019 (prior to and during the vaccination campaign) and 2022 surveys (after the vaccination campaign), we developed force of infection (FOI) models and estimated incidence and burden of CRS. RESULTS: In 2022, rubella seroprevalence was 85.2% (95% CI: 84.0, 86.2). Among 10 sites which participated in both rounds of serosurveys, the seroprevalence was not different between the two periods (pooled prevalence during 2017/2019: 83.5%, 95% CI: 82.1, 84.8; prevalence during 2022: 85.1%, 95% CI: 83.8, 86.3). The estimated annual incidence of CRS during 2017/2019 in India was 218.3 (95% CI: 209.7, 226.5) per 100, 000 livebirths, resulting in 47,120 (95% CI: 45,260, 48,875) cases of CRS every year. After measles-rubella (MR) vaccination campaign, the estimated incidence of CRS declined to 5.3 (95% CI: 0, 21.2) per 100,000 livebirths, resulting in 1141 (95% CI: 0, 4,569) cases of CRS during the post MR-vaccination campaign period. CONCLUSION: The incidence of CRS in India has substantially decreased following the nationwide MR vaccination campaign. About 15% of women in childbearing age in India lack immunity to rubella and hence susceptible to rubella infection. Since there are no routine rubella vaccination opportunities for this age group under the national immunization program, it is imperative to maintain high rates of rubella vaccination among children to prevent rubella virus exposure among women of childbearing age susceptible for rubella.