Metagenomic insights into fungal community composition of the nasopharyngeal region of COVID-19 associated mucormycosis patients from India.

Coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) was reported predominantly from India during the second wave of COVID-19  and has a high mortality rate. The present study aims to understand the fungal community composition of the nasopharyngeal region of CAM-infected individuals and compare it with severe COVID-19 patients and healthy controls. The fungal community composition was decoded by analyzing the sequence homology of the internal transcribed spacer-2-(ITS-2) region of metagenomic DNA extracted from the upper respiratory samples. The alpha-diversity indices were found to be significantly altered in CAM patients (p < 0.05). Interestingly, a higher abundance of Candida africana, Candida haemuloni, Starmerella floris, and Starmerella lactiscondensi was observed exclusively in CAM patients. The interindividual changes in mycobiome composition were well supported by beta-diversity analysis (p < 0.05). The current study provides insights into the dysbiosis of the nasal mycobiome during CAM infection. In conclusion, our study shows that severe COVID-19 and CAM are associated with alteration in mycobiome as compared to healthy controls. However, the sequential alteration in the fungal flora which ultimately leads to the development of CAM needs to be addressed by future studies.

Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end-of-TB-therapy. MATERIALS AND METHODS: This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-TB-therapy with symptom assessment, anti-Aspergillus IgG antibody and imaging of chest for diagnosing CPA. RESULTS: We recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end-of-TB-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end-of-TB-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-TB-therapy. CONCLUSIONS: CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies.

A study on the morbid histopathological changes in COVID-19 patients with or without comorbidities using minimally invasive tissue sampling.

COVID-19 causes morbid pathological changes in different organs including lungs, kidneys, liver, and so on, 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), had a malignancy (Gr 2), or had cardiometabolic conditions (hypertension, diabetes, or coronary artery disease) (Gr 3), postmortem tissue sampling (minimally invasive tissue sampling [MITS]) was done from the lungs, kidney, heart, and liver using a biopsy gun within 2 hours of death. Routine (hematoxylin and eosin) and special staining (acid fast bacilli, silver methanamine, periodic acid schiff) was done besides immunohistochemistry. A total of 100 patients underwent MITS and data of 92 patients were included (immunocompromised: 27, malignancy: 18, cardiometabolic conditions: 71). In lung histopathology, capillary congestion was more in those with malignancy, while others like diffuse alveolar damage, microthrombi, pneumocyte hyperplasia, and so on, were equally distributed. In liver histopathology, architectural 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 the heart was discerned. Certain histopathological features were markedly different in different groups (Gr 1, 2, and 3) of COVID-19 patients with fatal outcomes.

Outcomes of HFNC Use in COVID-19 Patients in Non-ICU Settings: A Single-center Experience.

How to cite this article: Aggarwal A, Arora U, Mittal A, Aggarwal A, Singh K, Ray A, et al.Outcomes of HFNC Use in COVID-19 Patients inNon-ICU Settings: A Single-center Experience. Indian J Crit Care Med 2022;26(4):528-530.

Artificial Intelligence-assisted chest X-ray assessment scheme for COVID-19.

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.

Effect of Training and Checklist Based Use of Ventilator Associated Pneumonia (VAP) Prevention Bundle Protocol on Patient Outcome: A Tertiary Care Centre Study.

OBJECTIVE: VAP prevention bundle includes daily sedation free interval, DVT prophylaxis, raising head end of bed, use of orogastric rather than nasogastric tube. This study aims to study the practices regarding VAP prevention bundle and its compliance, educating about the practices and effects on patients outcome. DESIGN: Quasi-experimental study, conducted in 3 phases. SETTING: Hospital based. PARTICIPANTS: Invasive Mechanically ventilated patients in the Department of Medicine of a tertiary care hospital. 50 patients included in phase 1 and 3. INTERVENTION: Phase 1 and Phase 3 were pre and post intervention phases respectively when compliance to VAP prevention bundle was assessed with intermediate Phase 2, the intervention phase where the residents and nurses were educated about VAP bundle through various means. A checklist was attached to patient records. OUTCOME MEASURES: Incidence of VAP, total hospital and ICU stay, duration of mechanical ventilation and mortality. RESULTS: On comparing the 2 phases, it was found that there was increase in the compliance to VAP bundle(p<0.001), use of orogastric tube (p<0.001) and use of daily sedation free interval (p<0.001). Statistically insignificant increase in the use of DVT prophylaxis (p= 0.996) and raising the head end of the bed (p=0.513), and decline in the number of days of ICU(p=0.804) and hospital stay(p=0.907), the duration of mechanical ventilation(p=0.909), mortality(p=0.315) and incidence of VAP(p=0.715) was noted. Among those who developed VAP, there was lower compliance to bundle. CONCLUSIONS: Practices like use of VAP prevention bundle improve on teaching efforts and use of checklist which improves patient care.

Chloroquine and Hydroxychloroquine for the Treatment of COVID-19: a Systematic Review and Meta-analysis.

BACKGROUND: There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. OBJECTIVE: We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19. METHODS: Two reviewers searched for published and pre-published relevant articles between December 2019 and 8 June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa Scale. The quality of evidence was graded as per the GRADE approach. RESULTS: We reviewed 12 observational and 3 randomized trials which included 10,659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46], time to fever resolution (mean difference - 0.54 days (- 1.19-011)) or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes. AUTHORS' CONCLUSION: The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.

Gargle lavage as a viable alternative to swab for detection of SARS-CoV-2.

BACKGROUND & OBJECTIVES: Nasopharyngeal and oropharyngeal swab (NPS and OPS) collection is widely accepted as the preferred method for obtaining respiratory samples. However, it has certain disadvantages which may be overcome by gargling. The primary objective of this study was to assess agreement between gargle lavage and swab as an appropriate respiratory sample for the detection of SARS-CoV-2. The secondary objective was to assess the patient acceptability of the two sampling methods. METHODS: It was a cross-sectional study done at a tertiary care hospital in New Delhi, India, on 50 confirmed COVID-19 patients. Paired swab (NPS and OPS) and gargle samples were taken within 72 h of their diagnosis. Samples were processed by reverse transcription-polymerase chain reaction (RT-PCR) for detection of SARS-CoV-2. Post-sample collection, a 10-point scale was administered to assess the level of discomfort with either of the collection methods. RESULTS: All gargle samples were positive and comparable to their corresponding swab samples irrespective of the symptoms and duration of illness. The cycle threshold (Ct) values for gargle samples were slightly higher but comparable to those of swabs. Bland-Altman plot showed good agreement between the two methods. Majority (72%) of the patients reported moderate-to-severe discomfort with swab collection in comparison to 24 per cent reporting only mild discomfort with gargle collection. INTERPRETATION & CONCLUSIONS: Our preliminary results show that the gargle lavage may be a viable alternative to swabs for sample collection for the detection of SARS-CoV-2. Adoption of gargle lavage for sample collection will have a significant impact as it will enable easy self-collection, relieve healthcare workers and also lead to substantial cost savings by reducing the need for swabs and personal protective equipment.

Efficacy and safety of antivirals for Covid-19: A systematic review and meta-analysis.

Background: Coronavirus disease 2019 (Covid-19) has led to a severe medical, social and economic crisis globally. Use of antivirals has given inconsistent results; thus systematic summaries of available evidence are required for any recommendations for treatment. We conducted a systematic review and meta-analysis on the use of antivirals for Covid-19. Methods: The databases we searched were-Medline, Embase, Cochrane CENTRAL and Medrxiv. Title/abstract screening, full-text screening and data abstraction were carried out in duplicate by two researchers. Pooled effect sizes and 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method of random effects for meta-analysis. Results: Twenty studies were found eligible for inclusion: 6 randomized controlled trials, 9 cohort studies and 5 case series. Moderate-quality evidence suggests a likely clinical benefit from the use of remdesivir in improving the number of recoveries (RR 1.18; 95% CI 1.07-1.31; I2 = 0%) and time to recovery in days (median -3.02; 95% CI -4.98 to -1.07; I2 = 97%). A possibility of lower mortality is suggested by low-quality evidence with remdesivir (RR 0.74; 95% CI 0.40-1.37, I2 = 58%). Moderate-quality evidence suggests no certain benefit of using lopinavir/ritonavir for Covid-19 compared to arbidol, lopinavir/ritonavir combined with arbidol or other medications used as controls. Conclusion: Further evidence from randomized controlled trials is required for all antivirals to treat Covid-19. At present, remdesivir seems more promising than other antivirals.

Convalescent plasma therapy for Covid-19: A systematic review.

Background: Covid-19 has emerged as a pandemic affecting more than 20 million people till date with few, if any, proven therapy. Convalescent plasma (CP) containing antibodies against the virus has been used with some success. We did a systematic review to synthesize the available data on CP therapy for treatment of Covid-19 to study the efficacy and safety outcomes. Methods: Two reviewers searched the published and pre-published literature between 1 January 2019 and 23 June 2020 for studies comparing the use of CP with standard therapy for Covid-19 patients. Data from the selected studies were abstracted and analysed for efficacy and safety outcomes. Critical appraisal of the evidence was done by using the Joanna Briggs Institute tool and the quality of evidence was graded as per GRADE. Results: We found 13 case series and 1 randomized trial that fulfilled our search criteria. Of the 12 case series with a total of 264 patients that reported the efficacy outcomes, 11 studies showed favourable results with survival benefit. The only RCT with 103 patients did not show any mortality benefit but was terminated early prior to complete enrolment. A single large study of 5000 patients reported safety outcomes and showed no major adverse events in patient streated with CP. Conclusion: There is very low-quality evidence to suggest efficacy and safety of CP in patients with Covid-19 infection. Well-designed randomized trials are urgently needed to provide robust data.

Anti-interleukin-6 therapies for Covid-19: A systematic review, critical appraisal and meta-analysis.

Background: . Coronavirus disease 2019 (Covid-19) has emerged as a pandemic by end-January 2020. Of the infected patients, 10%-15% may develop severe or critical illness. So far, no definite treatment is available for Covid-19. Cytokine release syndrome may underlie the pathogenesis of severe and critical disease. Anti-interleukin (IL)-6 therapies are being tried to improve clinical outcomes. Methods: . We did a systematic review to identify the available literature on anti-IL-6 therapies in the treatment of Covid-19 and used the GRADE method to assess the quality of evidence. Results: . Four case series and 10 case reports were identified. On critical assessment, we found that these studies reported some beneficial effect of anti-IL-6 therapy, but all the studies had a high risk of bias. The pooled estimate showed that 42% of patients improved but with a very wide confidence interval (CI) (95% CI 1%-91%) and substantial heterogeneity (I2 = 95%). The overall quality of evidence was graded as 'very low'. Conclusions: . Although promising, anti-IL-6 therapy for Covid-19 needs to be tested in randomized controlled trials to provide robust evidence.

Severe Immune Thrombocytopenia in a Patient with HIV-HCV Co-infection: Challenges in Management.

Immune thrombocytopenia is a well-known complication of both HIV and Hepatitis C virus infections. Management becomes challenging when a patient with HCV-HIV co-infection presents with severe thrombocytopenia. Adverse drug reactions and drug interactions has to be considered while choosing treatment options for such patients. We report such a case which illustrates the difficulty in managing severe thrombocytopenia in HCV-HIV co-infected patients where evidence based clinical decision making helped in choosing the right therapy for the patient.

Dengue Fever with Acute Disseminated Encephalomyelitis : Sensorium Imbroglio.

Dengue is the most common arboviral disease affecting many countries worldwide. With endemicity of the disease and huge burden, atypical clinical presentations occur posing high diagnostic and therapeutic dilemma. Emerging neurological complications in dengue fever are reported in recent past Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination and characterized by multifocal white matter involvement. Early suspicion and diagnosis of such complication is clinical dilemma and it further complicates the clinical scenario. This case report highlights occurrence of such uncommon manifestation of ADEM in commonly occurring dengue fever along with its diagnosis and successful management in a young individual.

Multi-drug Resistant Tuberculous Osteomyelitis of the First Carpometacarpal Joint Presenting as Unmasking Immune Reconstitution Inflammatory Syndrome.

Tuberculosis (TB) is an important cause of significant morbidity and mortality, particularly in patients living with human immunodeficiency virus (HIV ) infections. The co-infection of TB and HIV coinfection is further complicated by a relatively higher frequency of extra-pulmonary TB and upsurge of drug resistance. Musculoskeletal TB is a relatively less common form of extrapulmonary TB; involvement of carpometacarpal joint as an initial manifestation is even rarer. We herein present a retro positive patient who presented with low-grade fever, constitutional features and swelling of the base of the left thumb. On evaluation, he was found to have axillary and inguinal lymphadenopathy with lytic destruction of carpometacarpal joint as well as D10-D11 vertebrae. Fine needle aspiration (FNA) of synovial fluid was negative for tuberculosis but geneXpert from FNA of axillary node revealed Mycobacterium tuberculosis with rifampicin resistance. This case highlights the rarity of carpometacarpal joint involvement in TB as the initial manifestation and the importance of meticulous search of alternative sites for sampling in difficult situations such as osteoarticular TB. It also highlights the rising prevalence of drug-resistant TB and a definitive need for microbiological diagnosis wherever feasible.

B Cell ALL with Pyrexia of Unknown Origin, Masquerading as Inflammatory Arthritis.

ABSTRACT: We present a young male, with long standing fever, weight loss, bone pains, hepatosplenomegaly, cytopenias and severe joint pains. With normal peripheral smear and predominant joints involvement, he was started on corticosteroids. The partial response prompted the physician to continue the steroids. After some time, however, joints and bony pains worsened. After referral to us, he was found to have multiple bony lytic lesions and peripheral smear suggested B cell ALL. So, presentation predominantly with musculoskeletal symptoms, a normal peripheral smear and a partial therapeutic response to steroids as treatment of Systemic Juvenile Idiopathic Arthritis, delayed the diagnosis significantly leading to complications. So through our report we would like to stress that suspecting and diagnosing leukaemia early is important to prevent complications and resistance to treatment. An early bone marrow examination should also be instituted as a standard of care in peripheral smear negative patients.

Necrobiotic Xanthogranuloma as the Presenting Manifestation of Smouldering Myeloma.

Necrobiotic xanthogranuloma is a rare dermatological manifestation of underlying hematological malignancies, in particular, when associated with paraproteinemia. These patients who are clinically symptomatic with chronic papules, nodules or plaques which demonstrate a histopathological pattern suggestive of extensive and frequently confluent areas of necrobiosis with granulomatous infiltration, warrant evaluation for an underlying monoclonal gammopathy.

An Unusual Sequelae of Uncomplicated Vivax Malaria.

Albeit malaria is a common health problem in many parts of the world, the entity of post-malaria neurological syndrome (PMNS) is not well recognized. This is a rare entity of neurological and psychiatric manifestations described in patients with falciparum malaria which usually develops within 2 months of recovery from the illness. It has been reported in 1.2/1000 falciparum malaria cases, more commonly in those with severe disease. We report case of a 62-yrs-old male presenting with recurrent generalized seizures following adequately treated vivax malaria. Relevant investigations were done to rule out other differentials. The patient recovered completely reiterating the self-limiting course of PMNS. Occurrence of PMNS following uncomplicated vivax malaria is peculiar in this report.

Erythema Nodosum Leprosum as a Rare and Challenging Cause of Pyrexia of Unknown Origin.

A 30-year old male presented with fever for last 1 year. There were associated multiple painful skin eruptions with hyperpigmentation and scaling over whole body which had been progressively increasing. He also had anasarca along with generalized weakness. He presented to us in shock after an acute episode of gastroenteritis. After stabilization, he was evaluated for cause of fever. Routine fever workup (for typhoid, syphilis, malaria, filariasis, HIV, scrub typhus, leishmaniasis) was negative. CECT chest and abdomen revealed hepatosplenomegaly. There was no response to intravenous (IV) antibiotics and anti-fungal medications. Slit skin smears revealed 3+ acid fast bacilli (AFB). Skin biopsy revealed fragmented acid-fast bacilli with dense collection of neutrophils and foamy histiocytes in upper and middle dermis suggestive of Erythema Nodosum Leprosum (ENL). A diagnosis of ENL with lepromatous leprosy was made and patient started on steroids and thalidomide and subsequently on multidrug therapy (MDT). On therapy, patient's symptoms improved, and skin lesions resolved. Though Leprosy itself is a well-known common cause of PUO in India, its first presentation as ENL is rare and needs good index of suspicion and timely management.

A Catastrophic Presentation of Enteric Fever with Secondary Hemophagocytic Lymphohistiocytosis.

A 19 year old boy presented to the emergency room with fever of one week duration along with bleeding manifestations, few gastrointestinal symptoms, tachycardia, tachypnea and subtle encephalitic features. He was worked up for the usual causes of short duration fever, which proved inconclusive. In view of clinical worsening and cytopenias, a careful investigation process helped us in ruling out common etiologies for such a fever, alongwith unearthing the possibility of an underlying secondary hemophagocytic lymphohistiocytosis which led to severe thrombocytopenia and persistent high grade pyrexia. Widal test was positive in high titres, and patient was continued with antibiotics. Prompt treatment led to the uneventful recovery of the patient without any sequelae. Bleeding manifestations subsided, patient had rapid clinical improvement and was discharged after completing the course of antibiotics.

A Curious Case of Afebrile Dengue.

A 50-year-old male presented to us with features of diabetic ketoacidosis which was managed with adequate hydration and insulin therapy. His routine laboratory investigation revealed transaminitis, acute kidney injury and pancytopenia. Further evaluation for hematological and biochemical derangements uncovered positive dengue test (NS1 antigen and polymerase chain reaction assay). Patient distinctively reported no history of fever and remained afebrile during the course of illness. We report this case to highlight the possibility of afebrile dengue in endemic areas.