Mannose-binding lectin gene 2 variant DD (rs 5030737) is associated with susceptibility to COVID-19 infection in the urban population of Patna City (India).

The study aimed to measure plasma levels of Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) and their polymorphisms in COVID-19 patients and controls to detect association. As MBL is a protein of immunological importance, it may contribute to the first-line host defence against SARS-CoV-2. MBL initiates the lectin pathway of complement activation with help of MASP-1 and MASP-2. Hence, appropriate serum levels of MBL and MASPs are crucial in getting protection from the disease. The polymorphisms of MBL and MASP genes affect their plasma levels, impacting their protective function and thus may manifest susceptibility, extreme variability in the clinical symptoms and progression of COVID-19 disease. The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively.The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively. Our results indicate that median serum levels of MBL and MASP-2 were significantly low in diseased cases but attained normal levels on recovery. Only genotype DD was found to be associated with COVID-19 cases in the urban population of Patna city.

Evaluation of C4b as an adjunct marker in symptomatic RT-PCR negative Covid-19 cases.

Introduction: Detecting low viral load has been a challenge in this pandemic, which has led to its escalated transmission. Complement activation has been implicated in pathogenesis of Covid-19 infection. Thus, evaluation of complement activation in suspected Covid-19 infection may help to detect infection and limit false negative cases thus limiting transmission of infection. We speculate that measuring C4b, produced from an activated complement system due to the presence of Covid-19 may help in its detection, even when the viral titers are low. Methods: Plasma C4b levels of symptomatic RT-PCR positive patients (cases, n = 40); symptomatic RT-PCR negative patients (n = 35) and asymptomatic RT-PCR negative controls (n = 40) were evaluated. Plasma C5b-9, IL-6, D-dimer and C1-Inhibitor (C1-INH) were also measured in cases and controls. ELISA kits were used for all measurements. Statistical analyses were carried out using Stata, version 12 (Stata Corp., Texas, USA). Results: C4b levels were found to be significantly increased in RT-PCR positive patients as compared to asymptomatic RT-PCR negative controls. RT-PCR negative but symptomatic patients still showed increased C4b levels. The significantly higher levels of C4b in cases with a cut-off value of ≥ 116 ng/ml with optimum sensitivity and specificity of 80% and 52% respectively is indicative of its possible use as an adjunct marker. Increased levels of D-dimer, IL6, along with decreased levels of C1-INH were found in cases compared to controls. Whereas, C5b-9 levels were not significantly raised in cases. Conclusions: The results of our study suggests that plasma C4b may help to detect infection in false negative cases of RT-PCR that escape detection owing to low viral load. However, to confirm it a large-scale study is needed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01033-z.

Does Long-term Oxygen Therapy and Noninvasive Ventilation Predispose Rhino-orbital-cerebral Mucormycosis in COVID-19 Patients?

How to cite this article: Kumar A, Kumar A, Kumar N, Kumar A, Sinha C, Singh PK. Does Long-term Oxygen Therapy and Noninvasive Ventilation Predispose Rhino-orbital-cerebral Mucormycosis in COVID-19 Patients? Indian J Crit Care Med 2022;26(9):1063-1064.

Investigation of an acute surge of COVID-19 associated mucormycosis (CAM) cases reported to a tertiary health care institution in Bihar, India.

Introduction: Acute surge in coronavirus disease-2019 (COVID)-associated mucormycosis (CAM) cases was reported during mid-May 2021, which was later declared an epidemic in various states of India including Bihar. Objective: We carried out a rapid investigation of CAM cases to describe the epidemiological and clinical profiles and find plausible predictors to guide the initiation of public health actions. Methods: A team of public health specialists contacted all the CAM cases reported to our hospital to collect relevant information using a case-investigation-form. In addition, the team visited the Flu Clinic and Ear, Nose, and Throat (ENT) outpatient department (OPD) to capture CAM cases on daily basis during the period of the acute surge of CAM cases. Results: About 88% of 130 CAM cases reported during the period of the acute surge were in the advanced stage of mucormycosis. The majority of the CAM cases were younger (less than 60 years) [76.2%], diabetics [65.4%], un-vaccinated [86.9%], and had used steroids for management of COVID-19 [64.6%]. Other findings of public health importance were summarized and possible public health actions were recommended for the prevention of outbreaks in future. Conclusion: Optimum management of diabetes including screening for each COVID case, rational use of steroids only when necessary, strict adherence to COVID appropriate behavior by health professionals as well as the public, increasing COVID vaccine coverage, CAM awareness, and setting up a CAM surveillance mechanism may be the key to prevent and control CAM outbreaks in future.

Evaluation of C4b as an adjunct marker in symptomatic RT-PCR negative Covid-19 cases

Introduction Detecting low viral load has been a challenge in this pandemic, which has led to its escalated transmission. Complement activation has been implicated in pathogenesis of Covid-19 infection. Thus, evaluation of complement activation in suspected Covid-19 infection may help to detect infection and limit false negative cases thus limiting transmission of infection. We speculate that measuring C4b, produced from an activated complement system due to the presence of Covid-19 may help in its detection, even when the viral titers are low. Methods Plasma C4b levels of symptomatic RT-PCR positive patients (cases, n = 40);symptomatic RT-PCR negative patients (n = 35) and asymptomatic RT-PCR negative controls (n = 40) were evaluated. Plasma C5b-9, IL-6, D-dimer and C1-Inhibitor (C1-INH) were also measured in cases and controls. ELISA kits were used for all measurements. Statistical analyses were carried out using Stata, version 12 (Stata Corp., Texas, USA). Results C4b levels were found to be significantly increased in RT-PCR positive patients as compared to asymptomatic RT-PCR negative controls. RT-PCR negative but symptomatic patients still showed increased C4b levels. The significantly higher levels of C4b in cases with a cut-off value of ≥ 116 ng/ml with optimum sensitivity and specificity of 80% and 52% respectively is indicative of its possible use as an adjunct marker. Increased levels of D-dimer, IL6, along with decreased levels of C1-INH were found in cases compared to controls. Whereas, C5b-9 levels were not significantly raised in cases. Conclusions The results of our study suggests that plasma C4b may help to detect infection in false negative cases of RT-PCR that escape detection owing to low viral load. However, to confirm it a large-scale study is needed. Supplementary Information The online version contains supplementary material available at 10.1007/s12291-022-01033-z.

Clinicodemographic profile and predictors of poor outcome in hospitalised COVID-19 patients: a single-centre, retrospective cohort study from India.

OBJECTIVES: Primary objective was to study the clinicodemographic profile of hospitalised COVID-19 patients at a tertiary-care centre in India. Secondary objective was to identify predictors of poor outcome. SETTING: Single centre tertiary-care level. DESIGN: Retrospective cohort study. PARTICIPANTS: Consecutively hospitalised adults patients with COVID-19. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome variable was in-hospital mortality. Covariables were known comorbidities, clinical features, vital signs at the time of admission and on days 3-5 of admission, and initial laboratory investigations. RESULTS: Intergroup differences were tested using χ2 or Fischer's exact tests, Student's t-test or Mann-Whitney U test. Predictors of mortality were evaluated using multivariate logistic regression model. Out of 4102 SARS-CoV-2 positive patients admitted during 1-year period, 3268 (79.66%) survived to discharge and 834 (20.33%) died in the hospital. Mortality rates increased with age. Death was more common among males (OR 1.51, 95% CI 1.25 to 1.81). Out of 261 cases analysed in detail, 55.1% were in mild, 32.5% in moderate and 12.2% in severe triage category. Most common clinical presentations in the subgroup were fever (73.2%), cough/coryza (65.5%) and breathlessness (54%). Hypertension (45.2%), diabetes mellitus (41.8%) and chronic kidney disease (CKD; 6.1%) were common comorbidities. Disease severity on admission (adjusted OR 12.53, 95% CI 4.92 to 31.91, p<0.01), coagulation defect (33.21, 3.85-302.1, p<0.01), CKD (5.67, 1.08-29.64, p=0.04), high urea (11.05, 3.9-31.02, p<0.01), high prothrombin time (3.91, 1.59-9.65, p<0.01) and elevated ferritin (1.02, 1.00-1.03, p=0.02) were associated with poor outcome on multivariate regression. A strong predictor of mortality was disease progression on days 3-5 of admission (adjusted OR 13.66 95% CI 3.47 to 53.68). CONCLUSION: COVID-19 related mortality in hospitalised adult patients at our center was similar to the developed countries. Progression in disease severity on days 3-5 of admission or days 6-13 of illness onset acts as 'turning point' for timely referral or treatment intensification for optimum use of resources.

Clinico-Epidemiological Profile of Breakthrough COVID-19 Infection among Vaccinated Beneficiaries from a COVID-19 Vaccination Centre in Bihar, India.

BACKGROUND: When the whole world is fighting in an unprecedented pace against COVID-19 pandemic, the breakthrough COVID infections poise to dampen the rapid control of the same. We carried out this project with two objectives; first, to estimate the proportion of breakthrough COVID-19 infection among completely vaccinated individuals and second, to study the clinico-epidemiological profile of breakthrough COVID-19 infections among them. METHODS: This cross-sectional analytical study was conducted among 2703 fully vaccinated individuals from AIIMS, Patna COVID Vaccination Centre (CVC), Bihar, India. The participants were selected randomly using a systematic sampling technique from the list of beneficiaries maintained at the CVC. Telephonic interviews were made to collect the information by trained data collectors. RESULTS: A total of 274 fully vaccinated beneficiaries [10.1% (95% CI: 9.1%, 11.4%)] were diagnosed with breakthrough COVID-19 infection. The infections were more among males (10.4%) and the individuals aged ≤29 years (12.5%). The beneficiary categories, the healthcare-worker and the frontline-worker, were identified as predictors of the breakthrough COVID infections. Only one in three participants had adopted adequate COVID appropriate behaviour following the full vaccination. The majority of the breakthrough infections occurred during the second wave of COVID-19. The majority of the individuals with breakthrough infections were asymptomatic and no death was reported among them. CONCLUSION: One in every ten fully vaccinated individuals can get the breakthrough COVID infections. The healthcare-worker and the frontline-worker had independent risk of getting the breakthrough infections. Very few with breakthrough infections were serious and no death was reported among them.

Favourable outcome of severe COVID-19 patients in hyperinflammatory phase with high dose dexamethasone pulse therapy: A series of 10 cases.

The hyperinflammatory phase of COVID-19 occurring because of cytokine storm is the leading cause of mortality and morbidity in the affected patients. Various drugs with no definite cure are being tried to tackle the cytokine storm. Recently high dose corticosteroids are being used to arrest the surge of cytokines. In the current case series, we will be discussing the outcome of high dose dexamethasone pulse therapy in 10 cases of COVID-19 in hyperinflammatory phase who were cured of the disease along with improvement in laboratory parameters without any complications to the therapy.

Effectiveness of COVID-19 vaccine in preventing infection and disease severity: a case-control study from an Eastern State of India.

Effectiveness of corona virus disease-19 (COVID-19) vaccines used in India is unexplored and need to be substantiated. The present case-control study was planned to elicit the effectiveness of COVID-19 vaccines in preventing infection and disease severity in the general population of Bihar, India. This case-control study was conducted among people aged ≥45 years during April to June 2021. The cases were the COVID-19 patients admitted or visited All India Institute of Medical Sciences (AIIMS), Patna, Bihar, India, and were contacted directly. The controls were the individuals tested negative for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) at the Virology laboratory, AIIMS-Patna and contacted telephonically for collection of relevant information. The vaccine effectiveness (VE) was calculated by using the formula (VE = 1 - odds ratio). The adjusted VE for partial and full vaccination were estimated to be 52.0% (95% confidence interval (CI) 39.0-63.0%) and 83.0% (95% CI 73.0-89.0%) respectively for preventing SARS CoV-2 infection. The sub-group analyses of the cases have shown that the length of hospital stays (LOS) (partially vaccinated: 9 days vs. unvaccinated: 12 days; P = 0.028) and the severity of the disease (fully vaccinated: 30.3% vs. partially vaccinated: 51.3% and unvaccinated: 54.1%; P = 0.035) were significantly low among vaccinated compared to unvaccinated individuals. To conclude, four out of every five fully vaccinated individuals are estimated to be protected from contracting SARS CoV-2 infection. Vaccination lowered LOS and chances of development of severe disease.

Persistent positivity of SARS-CoV-2 nucleic acid in asymptomatic healthcare worker: infective virion or inactive nucleic acid?

Asymptomatic individuals positive for SARS-CoV-2 RNA constitute a significant proportion of the infected population and play a role in the transmission of the virus. We describe a healthcare worker who presented with fever and malaise and was diagnosed with mild COVID-19. The symptoms resolved within 4 days but there was persistent positivity of viral RNA in the upper respiratory tract for more than 58 days, which is the longest reported duration of persistence of SARS-CoV-2 in a healthcare worker. In this case report, we discuss clinical and administrative issues such as the role of asymptomatic cases in the transmission of the virus to patients and coworkers as an occupational hazard, interpretation of persistent positivity of nucleic acid test, duration of isolation and return-to-work guidelines pertinent to researchers and global health policymakers.