Spectrum of Fungal Infections in a Tertiary Care Centre of North India: Pre-COVID and COVID Scenario and Implications.

Background Rhino orbital mucormycosis is a rare and very aggressive entity. A sudden rise of this entity has been noticed with the insurgence of the COVID-19 pandemic both among immunocompromised and immuno-competent patients. This study was done to determine any possible correlation between these two deadly diseases. Materials and Methods This was a retrospective observational study done in the pathology department of a tertiary care center in North India over a three-year period (January 2019 - December 2021). Patient details along with relevant clinical data were retrieved from the patient's record file. Hematoxylin and eosin-stained slides of diagnosed cases were taken from the department records. Results A total of 45 patients (34 males, 11 females) were included in the study, seven of which were ophthalmic exenteration specimens. The mean age of the patients was 52.68 years. Fifteen cases showed COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) positivity. Histopathology revealed the presence of mucormycosis in all the cases. There were six cases showing granuloma formation and 14 cases revealed mixed fungal infection. Optic nerve involvement was seen in six cases of exenteration specimens. Conclusions The present study showed a sudden resurgence of secondary fungal infections, especially during the second wave of the COVID-19 pandemic. Associated co-morbid conditions and injudicious use of steroids and antibiotics have been the cause of depressed immunity leading to the infections. One must be aware of such co-infections to facilitate timely medical management to reduce morbidity and mortality.

A comprehensive overview of juvenile idiopathic arthritis: From pathophysiology to management.

Rheumatoid Arthritis (RA) is a progressive autoimmune disease. It is among the most widespread chronic illnesses in children, with an annual incidence of 1.6 to 23 new instances per 100,000 adolescents. About 1 child in every 1000 develops Juvenile Idiopathic Arthritis (JIA) type of chronic arthritis. The cause of JIA is not well known but what known is that it involves inflammation of the synovium and destruction of tissues in joints which can cause early-onset of oligo articular JIA. It is challenging to diagnose the condition in some children who initially complain of pain and joint swelling as there is no blood test discovered that can confirm the diagnoses of JIA. As JIA patients are immunosuppressed due to the use of drugs, making them vulnerable to catch infections like COVID-19 which can lead to cardiovascular diseases having high rate of morbidity and mortality. The comorbidity like Diabetes has higher incidence in these patients resulting in synergistic effect on inflammation. Currently, the connection of genetics in JIA provides evidence that HLA Class I and II alleles have a role in the pathophysiology of various subtypes of JIA which includes inflammation in the axial skeletal. The primary objective of therapy in juvenile idiopathic arthritis is the suppression of clinical symptoms. The pharmacological approach includes use of medications like DMARDs, NSAIDs etc. and non-pharmacological approach includes physiotherapy, which helps in restoring normal joint function and herbs as adjuvants which has the benefit of no side effects.

Quantification of diurnal variation in "glove hygiene" compliance in COVID ICUs: An exploratory study.

BACKGROUND: Hand hygiene compliance (HHC) monitoring is almost always done in daytime. Documentation of HHC in health care workers (HCWs) is limited during odd hours and nighttime. The objective of the study was to determine diurnal variation in HHC in different categories of health care workers in tertiary care hospital in North India. METHODS: A prospective, observational study was conducted in 3 COVID-19 intensive care units (ICUs) with closed-circuit television (CCTV) cameras. Dedicated infection control nurses monitored HHC among various HCWs (doctors, nursing staff, technicians, hospital and sanitary attendants) during day and nighttime, in 20-minute durations. The difference in HHC by-professional category and for each WHO moment was assessed using χ² test and P value. RESULTS: A total of 705 opportunities were observed over a period of 7 days, with overall compliance of 53%. Day and nighttime compliance was recorded to be 60.7% and 42.1%, respectively (P < .001). HCC was highest amongst resident doctors with little diurnal variation. However, nurses and housekeeping staff exhibited significant diurnal variation. The compliance at "after" moments was much higher than "before" moments in all professional categories. CONCLUSION: There was a significant decrease in compliance during nighttime, amongst all HCWs, with maximum variation exhibited by nursing staff. The present study underlines the importance of monitoring HHC at odd hours, to elicit a more accurate picture round the clock. Health care facilities monitoring compliance only during the daytime may substantially overestimate HHC.

Symptoms and psychosocial effects following hospitalization for Covid-19: A sequential, mixed-methods study from northern India.

Background It is reported that patients who have recovered from Covid-19 continue to experience various symptoms and adverse outcomes. However, this aspect has not been studied well. We aimed to evaluate these variables and the perceived impact of Covid-19 among patients discharged from a Covid hospital in northern India. Methods We conducted this study among patients discharged from a Covid-19 hospital in northern India in June 2020. As per the official policy at that time, patients detected to have Covid-19 (symptomatically or via contact tracing) were mandatorily admitted. A sequential, mixed-methods design was followed. Patients discharged from the hospital were contacted telephonically, and the cross-sectional prevalence of symptoms, the prevalence of depression and anxiety and the social consequences of admission were assessed. A subgroup of patients was interviewed for qualitative assessment of their experience. Results A total of 274 patients provided consent and were assessed, of which 8 patients underwent detailed interviews. The prevalence of somatic symptoms was 3.4%; 36.2% of the patients had depressive and 12% of the patients had anxiety symptoms. A majority of patients experienced adverse social and economic consequences of hospitalization for Covid-19. These themes were reinforced by a qualitative analysis of in-depth interviews. Conclusions Our study population experienced a high prevalence of adverse psychosocial consequences of Covid-19. These included depression and anxiety symptoms, stigma and economic and occupational consequences. These deserve more recognition and study.

Mucormycosis in COVID-19 pandemic and its neurovascular spread.

PURPOSE: Rhinocerebral mucormycosis is a rapidly progressive angioinvasive fungal infection commonly seen in diabetics. In the COVID-19 pandemic we have witnessed a sudden surge in these cases. We aimed to evaluate the disease presentation, patterns of spread, and any association with the COVID-19 virus. METHODS: This prospective study was conducted on mucormycosis patients operated between March and July 2021. The diagnosis was confirmed either on KOH staining, fungal culture or histopathological examination. RESULTS: Thirty one cases (21 males, 10 females) with a mean age of 53.3 years were included, of which 9 (29.1%) were COVID positive on presentation, 17 (54.8%) were post-COVID, while 5 (16.1%) had radiological evidence of COVID sequelae. Most common symptoms were cheek numbness (87.1%), headache (83.9%), visual disturbances (77.4%), and palate involvement (58.1%). Blackening of turbinates was uncommon (22.6%). Ethmoid sinus was involved in all patients. Pterygopalatine fossa involvement was present in 77.4%, and was accurately diagnosed on contrast enhanced MRI scan. There were 8 (25.8%) deaths, while the remaining are discharged or under treatment. CONCLUSION: An increase in the incidence of mucormycosis in the COVID-19 pandemic is probably due to a compromise in host immunity along with a synergistic effect in thrombotic microangiopathy. Spread of infection to the soft tissues of the infratemporal fossa, orbit or palate occur via neurovascular structures rather than by bone erosion. The pterygopalatine fossa is involved in most individuals.

Quantifying COVID-19 enforced global changes in atmospheric pollutants using cloud computing based remote sensing.

Global lockdowns in response to the COVID-19 pandemic have led to changes in the anthropogenic activities resulting in perceivable air quality improvements. Although several recent studies have analyzed these changes over different regions of the globe, these analyses have been constrained due to the usage of station based data which is mostly limited up to the metropolitan cities. Also the quantifiable changes have been reported only for the developed and developing regions leaving the poor economies (e.g. Africa) due to the shortage of in-situ data. Using a comprehensive set of high spatiotemporal resolution satellites and merged products of air pollutants, we analyze the air quality across the globe and quantify the improvement resulting from the suppressed anthropogenic activity during the lockdowns. In particular, we focus on megacities, capitals and cities with high standards of living to make the quantitative assessment. Our results offer valuable insights into the spatial distribution of changes in the air pollutants due to COVID-19 enforced lockdowns. Statistically significant reductions are observed over megacities with mean reduction by 19.74%, 7.38% and 49.9% in nitrogen dioxide (NO2), aerosol optical depth (AOD) and PM2.5 concentrations. Google Earth Engine empowered cloud computing based remote sensing is used and the results provide a testbed for climate sensitivity experiments and validation of chemistry-climate models. Additionally, Google Earth Engine based apps have been developed to visualize the changes in a real-time fashion.

Impact of single nucleotide polymorphisms in the OGG1 and XRCC1 genes on modulation of DNA damage in pesticide-exposed agricultural workers in Punjab, North-West India

Pesticide-induced DNA damage is primarily repaired by base excision repair (BER) pathway. However, polymorphism in DNA repair genes may modulate individual's DNA repair capacity (DRC) leading to increased genotoxicity and adverse health effects. Our first study in North-West Indian population aimed to evaluate the impact of OGG1 rs1052133 (Ser326Cys;C1245G), XRCC1 rs1799782 (Arg194Trp;C26304T) and XRCC1 rs25487 (Arg399Gln;G28152A) polymorphisms on the modulation of pesticide-induced DNA damage in a total of 450 subjects (225 pesticide-exposed agricultural workers and 225 age- and sex-matched controls). DNA damage was estimated by alkaline comet assay using silver-staining method. Genotyping was carried out by PCR-RFLP using site-specific restriction enzymes. Mann-Whitney U-test revealed elevation in DNA damage parameters (p <0.01) in pesticide-exposed agricultural workers than controls. Chi-square test showed significant (p <0.05) differences in the XRCC1 Arg194Trp (C26304T) and Arg399Gln (G28152A) genotypes among two groups. Multivariate logistic-regression analysis revealed that heterozygous genotypes of OGG1 rs1052133 (326Ser/Cys;1245CA), XRCC1 rs1799782 (194Arg/Trp;26304CT) and XRCC1 rs25487 (399Arg/Gln;2815GA) were positively associated (p <0.05) with elevated DNA damage parameters in pesticide-exposed agricultural workers. Our results strongly indicate significant positive association of variant OGG1 and XRCC1 genotypes with reduced DRC and higher pesticide-induced DNA damage in North-West Indian agricultural workers.

Structural Basis for Designing Multiepitope Vaccines Against COVID-19 Infection: In Silico Vaccine Design and Validation.

BACKGROUND: The novel coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to the ongoing 2019-2020 pandemic. SARS-CoV-2 is a positive-sense single-stranded RNA coronavirus. Effective countermeasures against SARS-CoV-2 infection require the design and development of specific and effective vaccine candidates. OBJECTIVE: To address the urgent need for a SARS-CoV-2 vaccine, in the present study, we designed and validated one cytotoxic T lymphocyte (CTL) and one helper T lymphocyte (HTL) multi-epitope vaccine (MEV) against SARS-CoV-2 using various in silico methods. METHODS: Both designed MEVs are composed of CTL and HTL epitopes screened from 11 Open Reading Frame (ORF), structural and nonstructural proteins of the SARS-CoV-2 proteome. Both MEVs also carry potential B-cell linear and discontinuous epitopes as well as interferon gamma-inducing epitopes. To enhance the immune response of our vaccine design, truncated (residues 10-153) Onchocerca volvulus activation-associated secreted protein-1 was used as an adjuvant at the N termini of both MEVs. The tertiary models for both the designed MEVs were generated, refined, and further analyzed for stable molecular interaction with toll-like receptor 3. Codon-biased complementary DNA (cDNA) was generated for both MEVs and analyzed in silico for high level expression in a mammalian (human) host cell line. RESULTS: In the present study, we screened and shortlisted 38 CTL, 33 HTL, and 12 B cell epitopes from the 11 ORF protein sequences of the SARS-CoV-2 proteome. Moreover, the molecular interactions of the screened epitopes with their respective human leukocyte antigen allele binders and the transporter associated with antigen processing (TAP) complex were positively validated. The shortlisted screened epitopes were utilized to design two novel MEVs against SARS-CoV-2. Further molecular models of both MEVs were prepared, and their stable molecular interactions with toll-like receptor 3 were positively validated. The codon-optimized cDNAs of both MEVs were also positively analyzed for high levels of overexpression in a human cell line. CONCLUSIONS: The present study is highly significant in terms of the molecular design of prospective CTL and HTL vaccines against SARS-CoV-2 infection with potential to elicit cellular and humoral immune responses. The epitopes of the designed MEVs are predicted to cover the large human population worldwide (96.10%). Hence, both designed MEVs could be tried in vivo as potential vaccine candidates against SARS-CoV-2.