Tracheostomy outcomes in coronavirus disease 2019: a systematic review and meta-analysis.

Tracheostomy is a standard surgical procedure that is used in critically ill patients who require sustained mechanical ventilation. In this article, we review the outcomes of coronavirus disease 2019 (COVID-19) patients who underwent tracheostomy. We searched for relevant articles on PubMed, Scopus, and Google Scholar, up to April 20, 2021. This meta- analysis examines ventilation liberation, decannulation, and hospital mortality rates in COVID-19 patients who have undergone tracheostomy. Two investigators evaluated the articles, and the differences of opinion were settled by consensus with a third author. A total of 4366 patients were included in 47 related articles for this meta-analysis. After data pooling, the proportions of ventilation liberation, decannulation and mortality were found to be 48% (95% CI: 31-64), 42% (95% CI: 17-69) and 18% (95% CI: 9-28) respectively. The Luis Furuya-Kanamori (LFK) index values for ventilation liberation, decannulation and mortality were 4.28, 1.32 and 0.69. No transmission of the disease attributable to participating in tracheostomy procedures was reported in most of the included articles.

Are we ready to manage an opioid epidemic in the intensive care unit?

The current opioid epidemic has had a massive impact on the critical care sector. This is due to an increase in the number of acute opioid overdose-related admissions and the number of opioid-dependent and opioid-tolerant patients admitted to intensive care units (ICUs). This review discusses the challenges that intensive care physicians face when caring for patients suffering from opioid-related disorders and analyses existing solutions. Preference for non-opioid analgesics, treatment of acute pain in the ICUs to avoid chronic pain syndrome, and education of patients and caregivers are critical to preventing this pandemic.

Assessment of the use and Safety of Protection Box for Intubation and Extubation Among Anaesthesiologists During COVID-19 Pandemic- A Cross-sectional Survey.

Introduction: Covid 19 epidemic has affected the people making them undergo emergency procedures requiring intubation. A protective box was innovated at our tertiary care centre to safeguard the HCW during intubation and/or extubation and the study was planned to assess its use and safety among the anaesthesiologists. Methods: A cross sectional, questionnaire base survey was done among anaesthesiologists in various strata of residency. The intubation box was used on the patient for intubation and extubation. The experience of participants was recorded via a Google Form and one response per participant was restricted. Participants were divided into two groups, Group 1(1stand 2nd year junior residents) and Group 2 (Senior resident and 3rd year junior resident). A valid response, was received from 25 anaesthesiologists who were either performing or assisting the intubation. The residents were evaluated based on the ease of use and safety features of the box. Results: There was a significant difference in the time taken to intubate between the two groups (p = 0.048) and it was found that Group 2 with more experience took less time to intubate than Group 1. Also, more respondents in Group 2 found it easier to manoeuvre the hands to handle instruments than Group 1(p = 0.024). Conclusion: We recommend that usage of intubation box during intubation or extubation is a non-harmful and necessary compromise that we must make to protect the /safeguard the well-being of Health Care Worker without affecting patient care in our fight with COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03692-7.

Comparison of clinical characteristics and outcome in RT-PCR positive and false-negative RT-PCR for COVID-19: A Retrospective analysis.

Cases with SARS-CoV-2 RT-PCR negative pneumonia are an understudied group with uncertainty remaining regarding their treatment approach. We aimed to compare the clinical and radiological characteristics of RT-PCR positive and clinically diagnosed RT-PCR negative COVID-19. This was a single-centre retrospective study conducted at a tertiary care hospital in Western India. All patients (age ≥18 years) with suspicion of COVID-19 with SARI (severe acute respiratory infections) who were subjected to RT-PCR testing (nasal/oropharyngeal swab) were included. Based on RTPCR results, patients were categorized and compared for demographic, clinical, and biochemical characteristics and outcomes. Out of 500 patients, 339 (67.8%) found RT-PCR positive. Except for the radiological findings, both groups differ in clinical presentation, disease severity (inflammatory markers), and outcome. RT-PCR-positive patients had raised ferritin, NLR (Neutrophil-Lymphocyte ratio), LDH, and high mortality compared to the swab-negative group. In-hospital mortality was also significantly high in RT-PCR positive group (HR=1.9, 95% CI=1.4-2.5, p=0.001). On multivariate analysis, NLR, ferritin, and d-dimer were the independent predictors of mortality in RT-PCR-positive (p=0.038, 0.054, and 0.023). At the same time, raised TLC (total leukocyte count) and procalcitonin were the risk factors for poor outcomes in RT-PCR-negative patients (p=0.041 and 0.038). We found significantly raised ferritin, NLR, and LDH levels and increased mortality in RT-PCR positive patients compared to RT-PCR negative. Incorporating clinical features, radiological, and biochemical parameters could be prudent while managing the RT-PCR-negative patients.

Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models

To combat future SARS-CoV-2 variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles presenting randomly-arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded, rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD-nanoparticles in mice and macaques, observing stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants including Omicrons and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest mosaic-8 RBD-nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers. Description

Basilar Artery Thrombosis in the Postpartum Period During COVID - 19 Pandemic: A Lethal But Avoidable Complication.

PURPOSE: To highlight the factors leading to the delayed diagnosis of basilar artery occlusion and poor outcome in the postpartum period during the prevailing Corona Virus Disease-2019 (COVID-19) pandemic. CASE REPORT: We here report a case of a 34-year female who presented with a headache localized to the occipital region after cesarean section under spinal anesthesia. Her headache severity increased over time, and she developed a generalized seizure episode and became unconscious. Subsequently, basilar artery thrombosis was diagnosed. Despite all efforts, she succumbed to death. We believe that we might have saved the patient's life if we could have made the diagnosis beforehand. CONCLUSION: We recommend that unless shown otherwise, postpartum headache and neck discomfort, even in individuals with no known risk factors, should have a low index of suspicion, early diagnosis using non-invasive radiological study such MRI to rule out this uncommon but deadly illness quickly.

Emerging mucormycosis posing threat to community: Anesthetist's perspective in a tertiary care center.

Mucormycosis has become an ever-growing threat to human health, particularly after the COVID-19 pandemic. As the number of cases of mucormycosis increased, it put a burden on anesthesiologists. Here we describe the etiopathogenesis, clinical presentation, and anesthesia management of patients suffering from mucormycosis.

Synthetic multiantigen MVA vaccine COH04S1 protects against SARS-CoV-2 in Syrian hamsters and non-human primates.

Second-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.

A Composite Study of Coagulation Milieu in Covid-19: Experience from a Tertiary Care Centre from India.

BACKGROUND: The understanding of pathogenesis is necessary for the development of effective treatment for COVID-19. Various studies have postulated that there is a complex interplay of mediators of coagulation and inflammation responsible for the pathogenesis of COVID-19. We did this study on coagulation parameters and inflammatory markers and their effect on outcome in patients with COVID-19. METHODS: This was a single centre observational cross-sectional study. Procoagulants [Prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, lupus anticoagulant (LA), fibrinogen, factor-VIII (F-VIII)]; anticoagulants [protein-C (PC), protein-S (PS), antithrombin] and inflammatory markers [interleukin-6 (IL-6) and highly sensitive - C-reactive protein (hs-CRP)] were measured at the time of hospitalization and correlated with the severity of the disease. RESULTS: A total of 230 patients were enrolled, of which 61.3%, 20.0%, and 18.7% had asymptomatic/ mild, moderate, or severe disease, respectively. COVID-19 disease severity was associated with rising trends with coagulation parameters (PT, APTT, D-Dimer; p value 0.01, <0.0001, <0.0001, respectively). Falling trends of anticoagulant (PC, Antithrombin; p value <0.0001, 0.003 respectively) and rising trends of procoagulant (fibrinogen, F-VIII; p value 0.004, <0.0001 respectively) were observed with increasing COVID-19 disease severity. Multivariate logistic regression analysis found that advanced age, high D-Dimer, and high hs-CRP (p value 0.035, 0.018, <0.0001 respectively) were independent predictors of mortality in COVID-19. Procoagulant parameters (D-dimer, APTT, Factor VIII) were positively correlated with anticoagulant parameters (PC and PS) and inflammatory parameters (hs-CRP). CONCLUSION: This study revealed increased levels of coagulation and inflammatory parameters, which correlated with the severity of COVID-19. Age, D-dimer, IL-6, hs-CRP, APTT, fibrinogen, and Factor VIII were significantly higher in patients with moderate and severe disease as compared to asymptomatic/mild disease. Advanced age, high D-dimer, and high hs-CRP were significantly associated with poor outcomes.

Clinical features and mortality in COVID-19 SARI versus non COVID-19 SARI cases from Western Rajasthan, India.

BACKGROUND: In March 2020, the Indian Council of Medical Research (ICMR) issued guidelines that all patients presenting with severe acute respiratory infections (SARI) should be investigated for coronavirus disease 2019 (COVID-19). Following the same protocol, in our institute, all patients with SARI were transferred to the COVID-19 suspect intensive care unit (ICU) and investigated for COVID-19. METHODS: This study was planned to examine the demographical, clinical features, and outcomes of the first 500 suspected patients of COVID-19 with SARI admitted in the COVID-19 suspect ICU at a tertiary care center. Between March 7 and July 20, 2020, 500 patients were admitted to the COVID-19 suspect ICU. We analyzed the demographical, clinical features, and outcomes between COVID-19 positive and negative SARI cases. The records of all the patients were reviewed until July 31, 2020. RESULTS: Of the 500 suspected patients admitted to the hospital, 88 patients showed positive results for COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR) of the nasopharyngeal swabs. The mean age in the positive group was higher (55.31 ± 16.16 years) than in the negative group (40.46 ± 17.49 years) (P < 0.001). Forty-seven (53.4%) of these patients in the COVID-19 positive group and 217 (52.7%) from the negative group suffered from previously known comorbidities. The common symptoms included fever, cough, sore throat, and dyspnea. Eighty-five (20.6%) patients died in the COVID-19 negative group, and 30 (34.1%) died in the COVID-19 positive group (P = 0.006). Deaths among the COVID-19 positive group had a significantly higher age than deaths in the COVID-19 negative group (P < 0.001). Among the patients who died with positive COVID-19 status had substantially higher neutrophilia and lymphopenia (P < 0.001). X-ray chest abnormalities were almost three times more likely in COVID-19 deaths (P < 0.001). CONCLUSION: In the present article, 17.6% of SARI were due to COVID-19 infection with significantly higher mortality (34.1%) in COVID-19 positive patients with SARI. Although all patients presenting as SARI have considerable mortality rates, the COVID-19-associated SARI cases thus had an almost one-third risk of mortality.

Mucormycosis: A Case Series of Patients Admitted in Non-COVID-19 Intensive Care Unit of a Tertiary Care Center during the Second Wave.

Rhino-orbital-cerebral mucormycosis is an invasive fungal infection associated with mortality of 25-62%. There has been a surge in the number of cases during this second wave of coronavirus disease-2019 (COVID-19) in India. We report 10 cases of mucormycosis admitted to our adult intensive care unit. After reviewing the patient's information, we found that 60% of patients had received steroids, and most had uncontrolled blood sugar levels. Most patients received treatment with surgical debridement and antifungal, although the mortality rate was as high as 40%. We report two unique cases of renal and gastrointestinal mucormycosis as well. We concluded that poor glycemic control was the primary etiology behind the rise in the number of cases. Our report also stresses the importance of early surgical intervention and suggests further research comparing the efficacy of combination antifungal therapy versus single antifungal (amphotericin B) to help resource-limited settings in these times of drug crisis. How to cite this article: Yadav S, Sharma A, Kothari N, Bhatia PK, Goyal S, Goyal A. Mucormycosis: A Case Series of Patients Admitted in Non-COVID-19 Intensive Care Unit of a Tertiary Care Center during the Second Wave. Indian J Crit Care Med 2021;25(10):1193-1196.

Clinical profile of bloodstream infections in COVID-19 patients: a retrospective cohort study.

BACKGROUND: Bloodstream infections (BSIs) are an emerging cause of significant morbidity and mortality in severe Coronavirus disease 2019 (COVID-19). We aimed to assess the prevalence, clinical profile and outcome of BSIs in critically ill COVID-19 patients. METHODS: This was a single-centre retrospective study conducted at a tertiary care hospital in Western India. All patients (age > 18 years) with reverse-transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 admitted in the intensive care unit (ICU) were included. Hospital electronic records were searched for demographic data, time of bloodstream infection since admission, clinical profile, antimicrobial resistance pattern and clinical outcome of all patients who developed BSIs. RESULTS: Out of 750 patients admitted in COVID ICU, 8.5% developed secondary BSIs. All severe COVID-19 patients who developed BSIs succumbed to illness. A significant proportion of BSIs were Gram-negative pathogens (53/64, 82.8%). Acinetobacter baumannii was the commonest isolate, followed by Klebsiella pneumoniae (32.8% and 21.9%, respectively). Multidrug-resistance organisms (MDRO) were found in 57.8% of the cases. The majority of MDRO belonged to K. pneumoniae and Enterococcus groups. The proportion of Gram-negative bacteria resistant to carbapenems was 47.2% (25/53). On multivariate analysis, raised total leukocyte counts, mechanical ventilation and presence of comorbidities were significantly associated with the incidence of BSIs. CONCLUSION: We found a significant prevalence of Acinetobacter baumannii in COVID-19 associated BSIs. The presence of comorbidities raised leukocyte counts and mechanical ventilation should alarm clinicians for possible BSIs. The timely initiation of empirical antibiotics and rapid de-escalation is vital to improve the outcome. At the same time, strict compliance of infection control practices should be accomplished to reduce the occurrence of MDRO.

30-Day Morbidity and Mortality of Bariatric Surgery During the COVID-19 Pandemic: a Multinational Cohort Study of 7704 Patients from 42 Countries.

BACKGROUND: There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates. METHODS: We conducted an international cohort study to determine all-cause and COVID-19-specific 30-day morbidity and mortality of BS performed between 01/05/2020 and 31/10/2020. RESULTS: Four hundred ninety-nine surgeons from 185 centres in 42 countries provided data on 7704 patients. Elective primary BS (n = 7084) was associated with a 30-day morbidity of 6.76% (n = 479) and a 30-day mortality of 0.14% (n = 10). Emergency BS, revisional BS, insulin-treated type 2 diabetes, and untreated obstructive sleep apnoea were associated with increased complications on multivariable analysis. Forty-three patients developed symptomatic COVID-19 postoperatively, with a higher risk in non-whites. Preoperative self-isolation, preoperative testing for SARS-CoV-2, and surgery in institutions not concurrently treating COVID-19 patients did not reduce the incidence of postoperative COVID-19. Postoperative symptomatic COVID-19 was more likely if the surgery was performed during a COVID-19 peak in that country. CONCLUSIONS: BS can be performed safely during the COVID-19 pandemic with appropriate perioperative protocols. There was no relationship between preoperative testing for COVID-19 and self-isolation with symptomatic postoperative COVID-19. The risk of postoperative COVID-19 risk was greater in non-whites or if BS was performed during a local peak.

Single-Cell RNA-seq Reveals Angiotensin-Converting Enzyme 2 and Transmembrane Serine Protease 2 Expression in TROP2+ Liver Progenitor Cells: Implications in Coronavirus Disease 2019-Associated Liver Dysfunction.

The recent coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 was first reported in China (December 2019) and is now prevalent across the globe. Entry of severe acute respiratory syndrome coronavirus 2 into mammalian cells requires the binding of viral Spike (S) proteins to the angiotensin-converting enzyme 2 receptor. Once entered, the S protein is primed by a specialized serine protease, transmembrane serine protease 2 in the host cell. Importantly, besides the respiratory symptoms that are consistent with other common respiratory virus infections when patients become viremic, a significant number of COVID-19 patients also develop liver comorbidities. We explored whether a specific target cell-type in the mammalian liver could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here, we used single-cell RNA-seq to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We analyzed ~300,000 single cells across five different (i.e., human fetal, healthy, cirrhotic, tumor, and adjacent normal) liver tissue types. This study reports on the co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 in a TROP2+ liver progenitor population. Importantly, we detected enrichment of this cell population in the cirrhotic liver when compared with tumor tissue. These results indicated that in COVID-19-associated liver dysfunction and cell death, a viral infection of TROP2+ progenitors in the liver might significantly impair liver regeneration in patients with liver cirrhosis.

Current Understanding of Novel Coronavirus: Molecular Pathogenesis, Diagnosis, and Treatment Approaches

An outbreak of “Pneumonia of Unknown Etiology” occurred in Wuhan, China, in late December 2019. Later, the agent factor was identified and coined as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the disease was named coronavirus disease 2019 (COVID-19). In a shorter period, this newly emergent infection brought the world to a standstill. On 11 March 2020, the WHO declared COVID-19 as a pandemic. Researchers across the globe have joined their hands to investigate SARS-CoV-2 in terms of pathogenicity, transmissibility, and deduce therapeutics to subjugate this infection. The researchers and scholars practicing different arts of medicine are on an extensive quest to come up with safer ways to curb the pathological implications of this viral infection. A huge number of clinical trials are underway from the branch of allopathy and naturopathy. Besides, a paradigm shift on cellular therapy and nano-medicine protocols has to be optimized for better clinical and functional outcomes of COVID-19-affected individuals. This article unveils a comprehensive review of the pathogenesis mode of spread, and various treatment modalities to combat COVID-19 disease.

Fostering mesenchymal stem cell therapy to halt cytokine storm in COVID-19.

The coronavirus disease 2019 (COVID-19) has been threatening the globe since the end of November 2019. The disease revealed cracks in the health care system as health care providers across the world were left without guidelines on definitive usage of pharmaceutical agents or vaccines. The World Health Organization (WHO) declared COVID-19 as a pandemic on the 11th of March 2020. Individuals with underlying systemic disorders have reported complications, such as cytokine storms, when infected with the virus. As the number of positive cases and the death toll across the globe continue to rise, various researchers have turned to cell based therapy using stem cells to combat COVID-19. The field of stem cells and regenerative medicine has provided a paradigm shift in treating a disease with minimally invasive techniques that provides maximal clinical and functional outcome for patients. With the available evidence of immunomodulatory and immune-privilege actions, mesenchymal stem cells (MSCs) can repair, regenerate and remodulate the native homeostasis of pulmonary parenchyma with improved pulmonary compliance. This article revolves around the usage of novel MSCs therapy for combating COVID-19.

Deciphering the SSR incidences across viral members of Coronaviridae family.

Presence of Simple Sequence Repeats (SSRs), both in genic and intergenic regions, have been widely studied in eukaryotes, prokaryotes, and viruses. In the current study, we undertook a survey to analyze the frequency and distribution of microsatellites or SSRs in multiple genomes of Coronaviridae members. We successfully identified 919 SSRs with length ≥12 bp across 55 reference genomes majority of which (838 SSRs) were found abundant in genic regions. The in-silico analysis further identified the preferential abundance of hexameric SSRs than any other size-based motif class. Our analysis shows that the genome size and GC content of the genome had a weak influence on SSR frequency and density. However, we find a positive correlation of SSRs GC content with genomic GC content. We also report relatively low abundances of all theoretically possible 501 repeat motif classes in all the genomes of Coronaviridae. The majority of SSRs were AT-rich. Overall, we see an underrepresentation of SSRs across the genomes of Coronaviridae. Besides, our integrative study highlights the presence of SSRs in ORF1ab (nsp3, nsp4, nsp5A_3CLpro and nsp5B_3CLpro, nsp6, nsp10, nsp12, nsp13, & nsp15 domains), S, ORF3a, ORF7a, N & 3' UTR regions of SARS-CoV-2 and harbours multiple mutations (3'UTR and ORF1ab SSRs serving as major mutational hotspots). This indicates the genic SSRs are under selection pressure against mutations that might alter the reading frame and at the same time responsible for rapid protein evolution. Our preliminary results indicate the significance of the limited repertoire of SSRs in the genomes of Coronaviridae.