A qualitative study on the psychological experience of caregivers of COVID-19 patients

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

Diagnoses of coronavirus disease 2019 (COVID-19) from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were first reported in December 2019. Since its emergence from the Chinese province of Wuhan, the World Health Organization (WHO) has announced 162 million confirmed cases of the SARS-CoV-2 infection worldwide, and reported roughly 3.3 million deaths as of May 16, 2021.1 Stratified by country, the United States leads with nearly 33 million confirmed COVID-19 cases, followed by India, Brazil, France, Turkey, and Russia.2 Structural firefighters perform essential public safety work and have continued that work despite the challenges of COVID-19. Career firefighters typically have long work schedules (24 or 48 hours on duty followed by multiple days off) and eat and sleep at the station as part of a team/shift. Firefighters respond to multiple hazards which include fires and rescues. In many localities, firefighters are dual trained as emergency medical service (EMS) personnel and provide emergency medical care. Because of their close living quarters and contact with the public, including rendering patient care and transporting patients, it is likely that firefighters are at an increased risk of infection with SARS-CoV-2. The fire service is aware of the risk of infection and has quickly adopted the increased use of personal protective equipment (PPE) and modified policies and procedures aimed at reducing the risk to firefighters.3,4 However, very little attention has been paid to occupational risks that may increase the severity of COVID-19 or to the potential long-term consequences of COVID-19 that may pose specific concerns for firefighters. The purpose of this review is to 1) outline the pathogeneses of COVID-19, 2) explore clinical and mechanistic links between COVID-19 and cardiovascular disease, 3) review known risk factors for COVID-19 complications and their prevalence among firefighters, and 4) consider steps that can be taken to better understand the long-term consequences of COVID-19 in the fire service. The review is limited to occupational factors for structural firefighters and does not cover wildland firefighters, although we acknowledge that COVID-19 may also present special concerns for wildland firefighters. PATHOGENESIS OF COVID-19 The SARS-CoV-2 virus enters the body predominantly via the lungs, and often results in pronounced respiratory symptoms. Thus COVID-19 was initially described as a respiratory disease. Indeed, respiratory failure from acute respiratory distress syndrome has been shown to be leading cause of COVID-19 induced mortality.5 A study by Guan et al6 reported that the majority of COVID-19 related consequences feature pneumonia and acute respiratory distress, which is consistent with other analyses suggesting that about 40% of COVID-19 patients develop acute respiratory distress syndrome, and 20% of these syndromes are severe.7 Wang et al8 showed that 61% of the individuals that required intensive care due to COVID-19 developed acute respiratory distress syndrome. COVID-19 not only lead to respiratory symptoms, but also underlying respiratory conditions increase the likelihood of experiencing severe symptoms. Meta-analyses revealed that the odds of severe COVID-19 infection were 5.69 times higher if individuals who have a history of chronic obstructive pulmonary disease.9 The virus requires the cooperation of two key proteins, TMPRSS2, and angiotensinogen converting enzyme 2 (ACE2) to infiltrate the body via the lung pneumocytes. TMPRSS2 is a key cellular regulator of coronavirus spike protein (S protein), with the S1 domain of the S protein responsible for receptor binding and the S2 domain controlling membrane fusion. Thus, coronavirus requires the binding of the S1 region to a cell surface receptor followed by the S2 subunit mediated fusion of the viral and cellular membranes in order to enter its host.10 This process requires S protein priming, or cleavage, by host proteases at the S1and S2 domains of the virus. This process has been described as a principle step for the cellular entry of SARS-CoV-2.11 Following S protein cleavage, Sars-CoV-2 binds to and enters lung cells via the enzyme ACE2, which is highly expressed in alveolar type 2 cells.12 Dissimilar to the original SARS-CoV, it has been suggested that SARS-CoV-2 may have a higher affinity to ACE2 positive cells in the upper respiratory tract, exacerbating its potent and detrimental effects.11 ACE2 is a membranous protein and importantly, an inactivator of angiotensin II (AngII). The binding of SARS-CoV-2 to ACE2 in lung cells promotes the endocytosis of the ACE2-SARS-CoV-2 complex, resulting in a reduction of membrane ACE2 abundance and an increase in serum AngII.12 Thus, SARS-CoV-2's affinity for ACE2 could explain its downstream effects on vascular parameters, including alterations in systolic and diastolic blood pressures, as elevated plasma AngII can increase blood pressure via aldosterone-mediated vasoconstriction and sodium and water retention on the kidneys.13 Furthermore, increased plasma AngII is associated with increased risks of myocardial infarction and left ventricular hypertrophy.13 In addition, SARS-CoV-2 promotes inflammation via the AT1R.12 The AngII-AT1R axis activates pro-inflammatory transcription factors NF-kB and STAT3, upregulating pro-inflammatory cytokines such as TNFa and IL-6 family cytokines,12,14 possibly leading to vascular inflammation and disease. Furthermore, recent studies suggest that the Sars-CoV-2 protein ORF3a encourages an aggressive inflammatory response via NF-κB activation, chemokine secretion, Golgi fragmentation, ER stress, and cell death.15 ORF3a can also inhibit type I interferon (type I IFN) signaling, downregulate major histocompatibility complex (MHC) class I expression, and reduce CD8+ cytotoxic T cell activity. Specifically, Siu et al15 demonstrated that ORF3a encourages the binding of TRAF3 to cytoplasmic portions of TNF receptors, promoting ubiquitination, and processing of p105 to p50. P50 is generated by TRAF3 ubiquitin-ligase ubiquitination of p150 and 26S proteasome-mediated removal of p105C terminal sequences. P50 then binds to RelA, RelB, or C-Rel subunits to produce functional NF-κB, a transcription factor essential for pro-IL-1β expression. The prevalence of pro-IL-1β transcripts is a requirement for NLRP3 inflammasome activation. Therefore, ORF3a-mediated p105 processing into p50 can help activate the NLRP3 inflammasome and lead to a robust inflammatory response.15 Siu et al further demonstrated ORF3a's ability to induce ASC polyubiquitination via a TRAF3 ubiquitin-ligase.15 ASC is the adapter complex of the NLRP3 inflammasome, and polyubiquitination of ASC provides a nondegradative signal necessary for ASC activation, caspase-1 activation, and mature IL-1β protein formation.15 Ultimately, the studies mentioned above illustrate how COVID-19 can target the cardiovascular system through its mode of entry and lead to vascular inflammation and dysfunction via upregulation of pro-inflammatory signaling. COVID-19 AND CARDIOVASCULAR DISEASE Although SARS-CoV-2 was first described as a respiratory disease, cardiac tissue and blood vessels express ACE2 receptors and appear to be particularly prone to COVID-19 infection.14 The heart, an ACE2 expressing tissue, was studied during the Toronto SARS outbreak (SARS-CoV), and investigators found evidence of SARS-CoV RNA in 35% of autopsied hearts.16 COVID-19 acts in a similar manner to the previous SARS-CoV, indicating that individuals with cardiovascular disease (CVD) are more prone to severe complications of SARS-CoV-2 compared to healthy individuals. Initial research on CVD-induced complications of COVID-19 was conducted in China. Wang et al investigated the association between biomarkers of CVD and the exacerbation of COVID-19 in hospitalized patients and found that cardiac injury, defined as either elevated high-sensitivity cardiac troponin I (hs-cTnI) or ECG/echocardiographic abnormalities, was present in 7.2% of the patients.8,17,19 The study also found that 22% of COVID-19 patients in ICU had biomarkers of cardiac injury.8,17 Zhou et al reported that hs-cTnI levels were at or greater than the 99th percentile upper reference limit in 46% of non-survivors, compared to only 1% of survivors who had levels this high.17,18 Thus, it has become apparent that COVID-19 can have severe cardiovascular consequences. Ultimately, it is also becoming clear that the presence of CVD, or CVD risk factors, can increase the likelihood of severe complications of COVID-19. The observational study by Zhou et al described above, also reported that 8% of patients (13% of non-survivors) had been diagnosed with CVD and 38% (48% of non-survivors) had been diagnosed with hypertension.17,18 Furthermore, Wang et al found that comorbidity of COVID-19 and CVD was prevalent in 15% (25% requiring ICU care) of patients analyzed, and Guan et al reported that 2.5% (9% among those with intubation or death) of COVID-19 patients also suffered from coronary artery disease.10,11,14 Chen et al demonstrated that in a cohort of 99 COVID-19 infected individuals at the Wuhan Jinyintan Hospital, 40% had some manifestation of cardiovascular or cerebrovascular disease.19 Other researchers have also reported on the higher prevalence of hypertension among COVID-19 patients; one study that although reports 15% of COVID patients had hypertension, 36% of those who needed intubation or suffered death had hypertension. Another study reported 31% of patients with COVID-19 had hypertension; however, 58% of patients requiring ICU care had hypertension.6,8 These findings demonstrate a clinical link between COVID-19 and CVD. EFFECT OF COVID-19 ON CARDIOVASCULAR SYSTEM Following the COVID-19 outbreak, researchers have begun to investigate the mechanisms associating COVID-19 and CVD. Emerging evidence strongly suggests the SARS-CoV-2 infection decreases myocardial functioning. Previous research has demonstrated that SARS-CoV, resembling both the structure and function of SARS-CoV-2, perturbates myocardial functioning.20 Recent research analyzing the cardiac manifestations of the SARS-CoV-2 infection found that the most common cardiac abnormality (39% of patients at baseline) was right ventricular dilation and dysfunction, followed by left ventricular diastolic and systolic dysfunction (16% and 10% of patients at baseline, respectively).21 In this study, 20% of these patients had clinical deterioration, with 60% of them having right ventricle deterioration and 25% having left ventricle systolic and diastolic deterioration.20 Thus, it appears that COVID-19, similar to other severe hypoxic respiratory illnesses, impairs cardiac function mostly by a right ventricular pressure overload state. Myocardial injury involves a pronounced escalation in pro-inflammatory cytokine secretions, which is commonly seen in COVID-19 patients. Specifically, research has found that patients suffering from COVID-19 had an upregulation of the pro-inflammatory cytokines IL1B, IFNγ, IP10, and MCP1. Individuals in ICU admission for COVID-19 had higher concentrations of the cytokines GCSF, IP10, MCP1, MIP1A, and TNFα than those not in ICU.22 An increase in these molecules due to COVID-19 severity can lead to an activation and dysregulation of T helper cells.22 Imbalances in (type 1 and type 2) T helper cells can lead to respiratory dysfunction, hypoxemia, and myocardial injury.20 Interestingly, Huang et al noticed that type 2 T-helper cell cytokines (IL4 and IL10), that suppress inflammation, were upregulated during infection of SARS-CoV-2.20 A study of competitive athletes recovering from COVID-19 found that 15% (4/26) had cardiovascular magnetic resonance findings suggestive of myocarditis despite only 2 of the 4 participants with findings suggestive of myocarditis having had COVID-19 symptoms.23 Acute thrombotic events are another major complication in individuals fighting the SARS-CoV-2 infection. Blood hypercoagulability has been shown to be common among hospitalized COVID-19 patients.24 Elevated D-Dimer levels, associated with thrombus formation and breakdown, are also reported in COVID-19 patients, worsening over the course of the disease.24 A review by Terpos et al elegantly describes how thrombus degradation products including PT and aPT are consistently upregulated in individuals requiring ICU admission.24 COVID-19 has also been shown to induce acute pulmonary embolisms in certain individuals,24–27 and one study found that 30% of COVID-19 patients had acute pulmonary embolus, measured by a CT coronary angiogram.28 This rate of pulmonary embolus is higher than what is usually seen in critically ill patients without COVID-19 (1.3%).28 Ultimately, COVID-19 patients are at higher risk for thromboembolic events, leading to adverse cardiovascular health risks. The endothelium plays key roles in regulating blood flow, maintaining hemostatic balance, and in immune response. Emerging evidence suggests that a vascular disease process contributes to COVID-19 pathogenesis.29 Several studies have begun to elucidate the role of endothelial dysfunction with COVID-19. Epithelial dysfunction, specifically pulmonary endothelial damage, is a common manifestation observed in patients infected with SARS Cov-2 virus and other coronaviruses.26 Endothelium damage due to COVID-19 is thought to occur by multiple mechanisms, including: a dysregulated immune response, enhanced vascular permeability, and exacerbated presence of pulmonary edemas.26,30 Varga et al31 demonstrated endothelial cell dysfunction in vital organs of individuals after becoming infected with COVID-19. These authors presented convincing evidence to indicate that the SARS CoV-2 virus has direct effects on endothelial cells, possibly due to the fact that ACE2 is also widely expressed on endothelial cells in multiple organs.14 Thus, it appears that recruitment of immune cells and pro-inflammatory cytokines due to ubiquitous expression of ACE2 can result in extensive endothelial dysfunction and cellular apoptosis. THE EFFECTS OF OBESITY ON CARDIOVASCULAR HEALTH AND COVID-19 Obesity has been recognized as an important predictor of CVD risk and adverse cardiorespiratory outcomes. Genetic and clinical experiments have found that that obesity is causally related to many disease states including hypertension, diabetes mellitus type 2, coronary heart disease, stroke, atrial fibrillation, renal disease, and heart failure.32 Others have reported that around 75% of hypertension can be attributed to obesity.33 It is clear that this obesity-induced hypertension leads to renal dysfunction due to an increased sympathetic nervous state and upregulated renin–angiotensin system.33 Obesity has effects on the infection and exacerbation of the SARS-CoV-2 infection. Sattar et al propose that obesity and ectopic fat deposition might reduce both optimal cardiorespiratory and immune response mechanisms, two major factors that can lead to severe manifestations of COVID-19.32 Several studies have reported on an association between obesity and COVID-19. Hamer et al reported a two-fold risk ratio of being infected with COVID-19 for obese individuals compared to normal weight individuals.34 These risk ratios were adjusted for age, sex, and mutually for each lifestyle, and physical inactivity. Furthermore, obesity was identified as the risk factor that contributed greatly to the prediction of COVID-19 infection risk. Finally, Hamer et al calculated a Population Attributable Fraction (PAF), which corresponds to the prevalence of risk factors in a population and the strength of its association with an outcome (COVID-19).34 The PAF used adjusted effect estimates on lifestyle factors (smoking, physical inactivity, overweight, and obesity) and COVID-19 and found that the total PAF for the three unhealthy lifestyle factors was 51.4%.34 Specifically, overweight and obesity had a PAF of 29.5%, smoking had a PAF of 13.3%, and physical inactivity had a PAF of 8.6%. Overall, it has become quite clear through both mechanistic and clinical research that there is a powerful effect of obesity on COVID-19 infection and severity. POTENTIAL RELATIONSHIPS BETWEEN FIREFIGHTERS AND COVID-19 As discussed through this paper, there is a strong relationship between both pulmonary disease, CVD and COVID-19. While initial research has focused on risk factors that place individuals at increased risk for COVID-19 complications, this section details ways that occupational exposures and cardiovascular risk factors that are known to be prevalent among firefighters, might make firefighters an occupational group that is at high risk of developing COVID-19 complications and for whom the long-term effects of COVID-19 infection might be particularly problematic. As summarized in Tables 1 and 2 and discussed in the following section, there are multiple factors that are known to exacerbate the rate of infection or severity of infection with SARS-CoV-2 and that are occupationally associated with firefighting. TABLE 1 - Association Between Medical Conditions of COVID-19 and Firefighting Medical Conditions COVID-19 Research Fire Service Research 1. Pulmonary disease • Significantly associated with a severe COVID-19 infection (OR 5.69, 95% CI: 2.49–13.00)9• 30% of studied COVID-19 patients developed acute respiratory distress syndrome,28 61% of studied COVID-19 patients developed acute respiratory distress syndrome,7,8,28 with approximately 20% of these cases being severe8 • Decrements in respiratory function were two-to-four-times greater in firefighters than general population35• Pulmonary function is associated with frequency of fire exposure36• Those who transitioned to less active assignments might not be protected from pulmonary disease88 2. Cardiovascular disease • 15–40% of patients had some manifestation of cardiovascular or cerebrovascular disease7,8,19 • Firefighters with other comorbidities demonstrated unfavorable CVD and cardiorespiratory fitness profiles70 COVID-19, coronavirus disease 2019; CVD, cardiovascular disease. TABLE 2 - Association Between Risk Factors of COVID-19 and Firefighting Risk Factors COVID-19 Research Fire Service Research 1. Age • Significant association of older age (≥65 years) and risk of COVID-19 mortality• Ranging from an OR of 3.76 (95% CI: 1.15–17.39; P = 0.023) to 4.59 (95% CI: 2.61–8.04; P < 0.001)57,58 • 9% of the entire US firefighting cohort is 60 years of age or older55 2. Sex • Males have made up as much as 60.3–70% of patients hospitalized with the SARS-CoV-2 infection• Prostatic diseases are associated with elevations in COVID-19 induced cardiac injury (OR 1.505, 95% CI; P = 0.046)60• In males, each standard deviation increase in free androgen escalates risk of severe COVID-19 manifestations (OR 1.22, 95% CI: 1.03–1.45; P = 0.024)60 • 96% of the US fire service is comprised of men, and more than half of US metropolitan departments have no women firefighters55,62 3. Hypertension • 56.6% of New York City area COVID-19 patients had hypertension59• Significant associate of COVID-19 mortality (pooled OR 2.70, 95% CI: 1.40–5.24; P = 0.003)57 • Up to 30% of the entire fire service have hypertension63,72• 46% of males and 29% of females firefighters had blood pressure the of 1 or 2 58% of firefighters and of firefighters have Obesity • been as the one of COVID-19 obese individuals are at greater risk for severe COVID-19 • of firefighters = were as either overweight or of overweight and obese firefighters may the US Cardiovascular • troponin is associated with COVID-19 mortality risk (OR 95% CI: P < cardiac injury in 7.2% of patients, and in 22% of ICU of patients had right ventricular dilation and dysfunction, had left ventricular diastolic dysfunction, 10% had systolic • Acute of decreases can induce ventricular and of myocardial and blood and • increased ACE2 and TMPRSS2 in alveolar type 2 cells and • Decrements in were more than the rate in were related to frequency of fire but not to age, smoking or Firefighters who a during fire a times greater rate of compared to COVID-19, coronavirus disease 2019; vital Pulmonary from recent study indicate that in the respiratory function of firefighters years) was two-to-four-times greater than the in the general reports with findings and also that the of pulmonary function in firefighters is associated with the frequency of fire of fires are more potent of than previous on their occupational firefighters appear to be at an increased risk of pulmonary is less evidence that firefighting leads to increased pulmonary disease, but this is a pulmonary disease is associated with increased risk for developing a severe COVID-19 infection. Pulmonary Risk and the acute and long-term effects of and is a in the fire service. have that and can reduce firefighters in 1 by lung function often to Furthermore, et demonstrated an of in firefighters following a of with 30% of the cohort having a in of Other studies have shown that the in which firefighters for and of can cause decreases in and vital as as in serum cell protein and serum studies the effects of long-term and on health have been the results are A study conducted on firefighters from the fire showed that in the and were not associated with of firefighting in active and that the protective respiratory equipment used by the fire service to be the detrimental effects of enhanced and In addition, a review of studies from to that the of and on health is and limited by of and that firefighters in pulmonary However, a study by et found that the in were more than the rate and was related to frequency of fire but not to age, smoking or et further showed that active firefighters a greater in compared to those who had or firefighters who a during fire a times greater rate of compared to Other studies have shown that with respiratory use in et showed that after years of there was a 10% in the of firefighters who to the World Thus, there is but not evidence that to and can both and pulmonary function in firefighters, use of respiratory protective equipment in the fire service. As pulmonary function is a robust to COVID-19 infection and severe COVID-19 Recent evidence also demonstrated that to can increase both ACE2 and TMPRSS2 in alveolar type 2 cells and due to firefighting might have a direct effect on COVID-19 but further research is Cardiovascular Risk Age cardiovascular health is by the prevalence of cardiovascular risk factors which can include age, sex, hypertension, and from that 9% of US firefighters are 60 years of age or Although a this of the fire service might have a more pronounced risk of COVID-19 infection than the general A recent observational study reported that age is one of the leading risk factors for infection and death due to Other studies have confirmed this that older individuals (≥65 years) have from to times higher risk of COVID-19 Cardiovascular Risk Sex suggests that males are more to a COVID-19 infection than with one study from the New York City area that males made up of the patients hospitalized with the SARS-CoV-2 A study in found that males made up of the patients on in the males were more in COVID-19 patients than in The in and COVID-19 infection is thought to be due to levels of between males and Specifically, TMPRSS2 expression has been shown to be by and androgen receptor which is a requirement for the transcription of et reported that related to androgen increased the odds of having troponin T levels induced cardiac by the et also found that free androgen associated with COVID-19 and severity in males, but not in among males who were for COVID-19, each standard deviation increase in free androgen increased the odds of a positive COVID-19 as as severe COVID-19 by The fire service is et reported that to of the US fire service is comprised of and more than half of US metropolitan departments have no women firefighters. Other that of firefighters and of firefighters are an occupational group by is most likely to be by the SARS-CoV-2, as higher androgen levels are found in Cardiovascular Risk Hypertension Hypertension is a risk factor of COVID-19 and CVD that is known to have a high prevalence the US fire service. Hypertension is reported to be one of the most common comorbidities related to COVID-19 infection. In et al found that hypertension was present in 56.6% of hospitalized COVID-19 patients the New York City A these that chronic hypertension, with other cardiovascular were more among patients than survivors (48% also suggests that hypertension is associated with COVID-19 and that individuals as have higher odds of from COVID-19 than a Research that approximately 20% to 30% of the entire fire service have recent study found that 46% of firefighters and 29% of females had blood pressure the of 1 or 2 Cardiovascular Risk Obesity As discussed obesity has been found to increase the risk of a COVID-19 infection. there is a high prevalence of obesity in the US fire service. have shown that obesity was present in of COVID-19 hospitalized Interestingly, work by et al a between age and body Thus, with pronounced obesity are at an increased risk of being infected with SARS-CoV-2. This is for the US fire as obesity is a major CVD risk factor found in firefighters. Obesity has also been found to increase the risk of coronary heart disease and links the mechanisms of vascular alterations to cardiac suggests that firefighters with high have vascular function and are at a greater risk for

Arterial stiffness and COVID-19: A bidirectional cause-effect relationship.

Perioperative Preparations for COVID-19: The Pediatric Cardiac Team Perspective

A<sc>bstract</sc>BackgroundTracheostomy is integral in long-term intensive care of coronavirus disease-2019 (COVID-19) patients. There is a paucity of studies on weaning outcomes and mortality after tracheostomy in COVID-19 in Indian scenario.Materials and methodsWe conducted a retrospective, single-center, observational study of severe COVID-19 patients who underwent elective tracheostomy (n = 65) during critical care in a tertiary care institute in Central India from May 1, 2020, to April 30, 2021. Data were collected from Medical records, ICU charts, and follow-up visits by patient. A primary objective was to study the clinical characteristics, tracheostomy complications, weaning outcomes, and mortality at 28 and 60 days of ICU admission. We categorized the cohort into two groups (deceased and survivor) and studied association of clinical parameters with 28-day mortality. Cox Proportional regression analysis was applied to calculate the hazard ratio among the predictors of mortality with p value <0.05 as significant.ResultsElective tracheostomy was done in 69 of 436 (15.8%) patients on invasive mechanical ventilation, of which 65 were included. Tracheostomy was percutaneous in 45/65 (69%) and surgical in 20/65 (31%) with timing from intubation as early in 41/65 and late in 24/65 with most common indication as weaning failure followed by anticipated prolonged ventilation. Tracheostomy complications were present in 29/65 (45%) patients with no difference in complication rates between timing and type of tracheostomy. Downsizing, decannulation, and weaning were successful in 22%, 32 (49%), and 35/65 (54%) patients after tracheostomy. The 28-day mortality was 30/65 (46%). The fractional inspired oxygen concentration (FiO2) requirement in survivors was lower (0.4–0.6, p = 0.015) with a higher PaO2/FiO2 ratio (118–200, p = 0.033). Early tracheostomy within 7 days of intubation was not associated with weaning or survival benefit.ConclusionsWe suggest that tracheostomy should be delayed to after 7 days of intubation, especially till FiO2 reduces to 0.5 with improvement in PaO2/FiO2 for better outcomes and avoiding a wasted procedure (CTRI/2021/07/034768).Study HighlightsTracheostomy is integral in care of COVID-19 patients needing prolonged ventilation. There is no difference in complications in early/late or percutaneous dilatational/surgical technique. We observed successful weaning post-tracheostomy in 54% patients. Mortality at 28 days was 46%. Early tracheostomy within 7 days of intubation did not improve weaning or survival.How to cite this articleKarna ST, Trivedi S, Singh P, Khurana A, Gouroumourty R, Dodda B, et al. Weaning Outcomes and 28-day Mortality after Tracheostomy in COVID-19 Patients in Central India: A Retrospective Observational Cohort Study. Indian J Crit Care Med 2022;26(1):85–93.

Responding to COVID-19: Perspectives From the Chinese Society of Gastroenterology

To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on insomnia and other sleep disturbances in health care professionals. A survey was distributed using social media and organizational emails to Brazilian active health care professionals during the COVID-19 outbreak. We explored potential associated factors including age, sex, occupation, workplace, work hours, income, previous infection with COVID-19, recent/current contact with COVID-19 patients, regional number of incident deaths, anxiety, and burnout. We evaluated new-onset/previous insomnia worsening episodes (primary outcome), new pharmacological treatments, sleep quality, duration, nightmares, and snoring (secondary outcomes). A total of 4,384 health professionals from all regions of the country were included in the analysis (44 ± 12 years, 76% females, 53.8% physicians). Overall, 55.7% were assisting patients with COVID-19, and 9.2% had a previous COVID-19 infection. The primary outcome occurred in 32.9% of respondents in parallel to 13% new pharmacological treatments for insomnia. The sleep quality worsened for 61.4%, while 43.5% and 22.8% reported ≥ 1-hour sleep duration reduction and worsening or new-onset nightmares, respectively. Multivariate analyses showed that age (odds ratio [OR]: 1.008; 95% confidence interval [CI] 1.001-1.015), females (OR: 1.590; 95% CI 1.335-1.900), weight change (decrease: OR: 1.772; 95% CI 1.453-2.161; increase: OR: 1.468; 95% CI 1.249-1.728), prevalent anxiety (OR: 3.414; 95% CI 2.954-3.948), new-onset burnout (OR: 1.761; 95% CI 1.489-2.083), family income reduction > 30% (OR: 1.288; 95% CI 1.069-1.553), and assisting patients with COVID-19 (OR: 1.275; 95% CI 1.081-1.506) were independently associated with new-onset or worsening of previous insomnia episodes. We observed a huge burden of insomnia episodes and other sleep disturbances in health care professionals during the COVID-19 pandemic. Drager LF, Pachito DV, Moreno CRC, etal. Insomnia episodes, new-onset pharmacological treatments, and other sleep disturbances during the COVID-19 pandemic: a nationwide cross-sectional study in Brazilian health care professionals. J Clin Sleep Med. 2022;18(2):373-382.

Role of Ultrasound-Guided Evaluation of Dyspnea in the Coronavirus Disease 2019 Pandemic

Coronavirus disease 2019 (COVID-19) is a new variant of disease which has never been identified in human beings and is a communicable respiratory tract disease, it is very harmful to people, especially to nurses since not all healthcare workers in a hospital are equipped with Personal Protective Equipment (PPE) due to its limited availability in Indonesia. The objective of the research is to explore the experience of nurses who do not take care of patients COVID-19 patients in a hospital during COVID-19 pandemic. The research employs qualitative method with descriptive phenomenological approach. The participants are 10 nurses who do not take care of COVID-19 patients at USU hospital, selected by nursing purposive sampling technique. The data are collected through in-depth interviews. All interviews are firstly recorded and then transcribed. They are analyzed by using Colaizzi test approach. The result of the thematic analysis finals six themes: that the nurses have psychological impact, have COVID-19 pandemic impact, encounter obstacles during the pandemic, carry out coping mechanism, develop strategies in handling COVID-19, and receive social support. It is concluded that nurses experience psychological impact in the beginning of the pandemic such as excessive anxiety and stress so that they need social support from families, colleagues, or neighbors. The nurses knowledge of COVID-19 is still poor, so that it is necessary to provide more profound seminars and training.

Cardiac surgery and the coronavirus disease 2019 pandemic: What we know, what we do not know, and what we need to do

To the Editor: The global pandemic of coronavirus disease 2019 (COVID-19) is not under control, and COVID-19 has affected tens of millions of people worldwide. Although the main features of COVID-19 are diffuse alveolar damage and acute respiratory failure, damage to other organs is also of concern because these patients tend to have more severe symptoms and worse prognosis. In this article, we briefly review the characteristics of kidney involvement in COVID-19 and the impact of kidney injury on prognosis of the disease, in order to better understand the COVID-19 epidemic from the perspective of a nephrologist. The respiratory system is not the only target organ of COVID-19, as the most important organs of the metabolic and excretory system, kidneys have been shown to be involved in COVID-19. According to the current literature, some patients manifested with kidney injury, such as hematuria, proteinuria, serum creatinine (Scr) fluctuations or even acute kidney injury (AKI). The incidence of kidney involvement in the patients with COVID-19 varies from different studies, depending on the proportion of severe patients. In addition, the patients with COVID-19 who already have kidney disease are more likely to develop kidney injury, and the renal functions are more likely to be damaged if the COVID-19 patients are in critical condition. Meanwhile, kidney damage will deteriorate the progress of COVID-19, leading to poor prognosis and higher mortality. In the early stages of the COVID-19 outbreak, the high incidence of kidney damage in critically ill patients may be due to lack of clinical experience and shortage of medical resources. Retrospective data from the Wuhan Tongji Hospital reported an association between abnormal kidney function and mortality in the hospitalized COVID-19 patients. In this cohort, 701 patients were admitted, including 297 (42.4%) severe patients, and 113 (16.1%) of these patients died in the hospital. The incidences of proteinuria, hematuria, and elevated Scr were 43.9%, 26.7%, and 14.4%, respectively. In addition, 13.1% of patients had estimated glomerular filtration rate levels under 60 mL·min−1·1 73 m−2, and 5.1% of patients suffered from AKI during hospitalization. Patients with elevated baseline level of Scr were more likely to develop AKI (11.9% vs. normal baseline Scr 4.0%) and had more severe diseases, and further analysis indicated that patients with impaired renal function had higher risk for in-hospital mortality rate.[1] Yang et al[2] observed the clinical course and outcomes of 52 critically ill adult patients with COVID-19 who were admitted to the intensive care unit (ICU) with a mean age of 59.7 years. In total, 15 (28.8%) patients suffered from AKI, and 32 (61.5%) patients died. Compared to survivors, non-survivors were older and more likely to develop acute respiratory distress syndrome (ARDS) (26 [81%] vs. 9 [45%]) and AKI (12 [37.5%] vs. 3 [15%]). Another study showed that 36.6% of patients suffered from AKI in the 5449 patients with COVID-19, and the proportion of using ventilators was as high as 89.7% in the patients with AKI.[3] The above clinical evidence showed that the incidence of renal impairment is high in hospitalized critically ill COVID-19 patients and is also closely related to in-hospital death. However, the mild to moderate COVID-19 does not commonly result in AKI. According to first-line data, there is no kidney involvement in most patients with mild COVID-19 symptoms. Wang et al[4] analyzed the clinical characteristics of 138 hospitalized COVID-19 patients, only five (3.6%) patients suffered from AKI and three of them were in critical condition, indicating that kidney impairment was not common in these patients. The renal pathological changes in the COVID-19 patients usually presented with swollen glomerular endothelial cells, a small amount of protein exudate in the glomerular Bowman capsule, and transparent thrombosis in intra-capillaries. Moreover, edema, vacuolar degeneration, and shedding of renal tubular epithelial cells were observed. Protein casts and pigment casts were observed in the lumen, and renal interstitial hyperemia, microthrombosis and focal fibrosis were also observed. A few reports showed that novel coronavirus particles could be seen in the tubular epithelial cells and podocytes. It implied that the novel coronavirus may damage the kidney directly.[5] However, from our experience, the causes of kidney injury in the COVID-19 patients may be mainly due to the clinical secondary factors, that is, renal damage caused by infection, hypoxemia, hemodynamic instability, and other comprehensive factors. Other risk factors of AKI in the COVID-19 also have been reported, such as high expression of angiotensin-converting enzyme 2 (ACE2) in the kidney, inflammation, and cytokines, but these mechanisms need to be further verified. In most patients with COVID-19, kidney injury only manifested with mild elevation of Scr or blood urea nitrogen. Nausea, vomiting, anorexia, malnutrition, insufficient intake of calories, and insufficient blood volume may attribute to the temporary abnormal renal function. The incidence of AKI increased in the critically ill patients with COVID-19 may be attributed to secondary injury, such as hypoxemia, severe infection, acid-base electrolyte balance disorder, and hemodynamic instabilities, including hypotension and infection-induced septic shock or high-dose vascular active drugs-induced renal hypoperfusion. Inflammation and cytokine storm-mediated kidney injury may be another potential mechanism of AKI. Current data showed that there were higher plasma levels of interleukin (IL)-2, IL-7, IL-10, granulocyte colony-stimulating factor, inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein-1 alpha, and tumor necrosis factor in the critical patients with COVID-19. Cytokine release syndrome (CRS) may also induce the kidney damage through increased vascular permeability under the conditions with inflammation, insufficient effective circulating blood volume, hypotension, and endothelial cell damage.[6] It is believed that the novel coronavirus enters cells mainly by binding to ACE2 receptors on the cell surface through its envelope-anchored spike (S) protein. The transmembrane protease serine (TMPRSS) family acts as key cellular proteases in coronavirus S protein priming, which plays an important role after coronavirus enters cells. Therefore, cells with ACE2 expression may act as target cells of the novel coronavirus. It is reported that kidney proximal tubule cells exhibit significantly high ACE2 expression with an approximate proportion of ACE2-positive cells of 4%. Researchers also identified that ACE2 and TMPRSS genes are significantly co-expressed in glomerular podocytes and renal proximal convoluted tubules, and the expression level of ACE2 in the kidneys of Westerners is higher than that of Asians, suggesting that Western COVID-19 patients may be more likely to develop AKI. Proteinuria as a typical clinical symptom in the patients with COVID-19 may be due to podocyte damage.[7] There is not any definite targeted treatment for COVID-19 until now. The prevention and control approaches to this disease include controlling the source of infection, strengthening personal protection to reduce the risk of transmission, early diagnosis/isolation, and symptomatic supportive care for the confirmed patients. In the treatment of COVID-19 patients with kidney involvement, early detection, and protection of kidney function are important to reduce mortality and improve the prognosis of the critically ill patients. Strategies include adequate hemodynamic support, avoidance of nephrotoxic drugs, and renal replacement therapy if it is necessary. The proportion of continuous renal replacement therapy (CRRT) in COVID-19 patients ranged from 1.5% to 9.0%, and the proportion of CRRT in severe and critically ill patients admitted to ICU ranged from 5.6% to 23%.[6] In a group of COVID-19 patients with invasive mechanical ventilation, up to 61.1% patients need to receive CRRT. Extracorporeal therapies may help to remove cytokines and prevent CRS-induced organ damage. Applicable blood purification modes include hemoperfusion, plasma adsorption or high-dose CRRT with high cut-off membranes.[6] With regard to the prognosis of COVID-19, 3.4% to 41.8% of COVID-19 patients suffered from ARDS, whereas 7.4% to 32.8% of COVID-19 patients received mechanical ventilation treatment (including non-invasive and invasive). In addition, 5.0% to 31.7% of COVID-19 patients were admitted to the ICU, and the mortality rate of critically ill COVID-19 patients reached 63.9%.[1–4,6] Kidney involvement is associated with poor prognosis of COVID-19. Patients with AKI have a higher mortality rate compared to patients without AKI. In a population of 1099 laboratory-confirmed COVID-19 patients, AKI occurred only in six patients, but unfortunately an endpoint event (admission to ICU, use of mechanical ventilation, or death) was triggered in four of these patients. These data suggest that the prognosis of the patient is poor once AKI occurs.[6] In addition, the abnormalities of urine sediment tests, such as proteinuria and hematuria, also indicate a poor prognosis for the patient. Research data analysis indicated that increased baseline Scr/urea nitrogen, peak Scr >133 μmol/L, AKI, proteinuria, and hematuria were shown to be independent risk factors for the mortality of the patients with COVID-19.[1] Overall, kidney involvement in patients with COVID-19 usually manifested with hematuria, proteinuria, or mild fluctuations in renal function, and changes in renal function are causal and harmful. Meanwhile, critically ill patients are much more prone to suffer from AKI followed by poor prognosis. For these patients, clinicians need to closely monitor changes in renal function, and early diagnosis and active treatment may reduce the incidence of AKI and the mortality rate. Acknowledgements The authors thank all the medical, nursing, and technical staff of Central Theatre Command (CTC) General Hospital, who worked together with Dr. Qing-Li Cheng, and served for the critically ill patients with COVID-19 during the epidemic in Wuhan city, China. Funding This work was supported by grants from the Open Fund of National Clinical Research Center for Geriatric Diseases (No. NCRCC-PLAGH-2018012 and ZXBJ2001); the National Natural Science Foundation of China (Youth program No. 81600655) and Health Care Program Foundation of PLA General Hospital (Key Project No. NLBJ-2019006). Conflicts of interest None.

Second wave of COVID-19 pandemic and the surge of mucormycosis: Lessons learnt and future preparedness: Indian Society of Anaesthesiologists (ISA National) Advisory and Position Statement.

Free Papers Compiled

Pre-admission anticoagulant therapy and mortality in hospitalized COVID-19 patients: A retrospective cohort study

Pharmacological rationale for antihypertensive drug choice on COVID-19-affected patients: ACEI/ARB might not increase their susceptibility.