Impact of congenital heart disease on outcomes among pediatric patients hospitalized for COVID-19 infection.

BACKGROUND: COVID-19 infection is generally regarded as an acute self-limiting illness in children, but it can cause significant morbidity and mortality in both healthy and high-risk children. There are limited data on the outcomes of children with congenital heart disease (CHD) and COVID-19. This study aimed to examine the risks of mortality, in-hospital cardiovascular and non-cardiovascular complications in this patient population. METHODS: We analyzed data from hospitalized pediatric patients from 2020 using the nationally representative National Inpatient Sample (NIS). Children hospitalized for COVID-19 were included, and weighted data were used to compare in-hospital mortality and morbidities between children with and without CHD. RESULTS: Out of 36,690 children admitted with a diagnosis of COVID-19 infection(ICD-10 code:U07.1 and B97.29) during calendar year 2020, 1240 (3.4%) had CHD. The risk of mortality in children with CHD was not significantly higher than those without CHD(1.2% vs. 0.8%, p = 0.50), with adjusted OR (aOR) of 1.7 (95% CI: 0.6-5.3). Tachyarrhythmias and heart block were more likely in CHD children with an aOR of 4.2 (95% CI: 1.8-9.9) and aOR of 5.0 (95% CI: 2.4-10.8), respectively. Similarly, respiratory failure [aOR = 2.0 (1.5-2.8)], respiratory failure requiring non-invasive mechanical ventilation [aOR = 2.7 (1.4-5.2)] and invasive mechanical ventilation [aOR = 2.6 (1.6-4.0)], and acute kidney injury [aOR = 3.4 (2.2-5.4)] were all significantly higher among patients with CHD. Median length of hospital stay in children with CHD was longer than those without CHD [5 days (IQR: 2-11) vs. 3 days (IQR: 2-5), p = < 0.001]. CONCLUSIONS: Children with CHD hospitalized with COVID-19 infection were at increased risk of serious cardiovascular and non-cardiovascular adverse clinical outcomes. They also had increased length of hospital stay and utilization of healthcare resources.

The effects of high-flow oxygen therapy on mortality in patients with COVID-19.

BACKGROUND: High-flow oxygen therapy (HFOT) has been successful in treating acute hypoxic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS). Successful treatment with noninvasive ventilation and avoidance of mechanical ventilation (MV) has been associated with decreased mortality and positive patient outcomes. It is unclear whether the evidence supports the use of HFOT to treat coronavirus disease 2019 (COVID-19)-induced AHRF and ARDS. OBJECTIVES: To determine whether the use of HFOT decreases the need for intubation or decreases mortality compared with MV in patients with AHRF due to COVID-19. DATA SOURCES: A literature search was conducted in March 2022 using CINAHL, Embase, PubMed, and Scopus bibliographic databases. Ten studies comparing HFOT and MV in COVID-19 respiratory failure met inclusion criteria. CONCLUSIONS: Nine studies found a statistically significant reduction in the need for intubation; eight studies found significantly decreased morality in patients who received HFOT. Study design and methodologies limited the findings. IMPLICATIONS FOR PRACTICE: Based on the available evidence, the use of HFOT positively affected mortality and incidence of the need for intubation and MV. Further research needs to be conducted before HFOT is adopted as the standard of care for COVID-19-induced AHRF and ARDS. Nurse practitioners should be informed regarding the various respiratory support modalities and evaluate risk versus benefit when caring for patients with COVID-19-induced AHRF and ARDS.

Clinical presentation of COVID-19 and association with outcomes among hospitalized older adults.

BACKGROUND: Older adults from racial and ethnic minority groups are at higher risk for worse outcomes with COVID-19. This study sought to characterize the symptomatology of COVID-19 and the association of symptoms with all-cause in-hospital mortality and respiratory failure in a cohort of older, predominantly African American adults admitted to a tertiary hospital. METHODS: A retrospective chart review of all hospitalized patients 65 and older with a positive SARS-CoV-2 test was conducted in a 953-bed academic, urban hospital. Measurements included demographics, symptoms, laboratory findings, and outcomes. The primary outcome was in-hospital mortality, and the secondary outcome was respiratory failure. RESULTS: A total of 134 patients with a mean age of 76.4 years were studied. Fifty-six percent were men and 90% were African American. Of these, 108 patients presented with typical symptoms, among whom 89.8% had co-existing geriatric syndromes. Only 10.2% presented with typical symptoms alone. The most common typical symptoms were fever (57%), shortness of breath (SOB) (51.2%), and cough (48.8%). Atypical symptoms were present in 68 (51%) patients, of whom 83.8% had co-existing typical symptoms and 76.5% had co-existing geriatric syndromes. Only 17.2% of patients presented with atypical symptoms alone. Atypical symptoms identified were anorexia (43%), dizziness (12.4%), and syncope (7.4%). Geriatric syndromes were identified in 102 (76%) patients, including altered mental status (71.1%), weakness (26.4%), and falls (24.8%). Respiratory failure occurred in 65.8% of patients, with 35.4% requiring ventilators while 22.3% of patients died. Age, male gender, SOB, sepsis, and certain laboratory values were associated with outcomes. CONCLUSION: Hospitalized older adults infected with SARS-CoV-2 may present with a range of symptoms encompassing typical, atypical, and geriatric syndromes. Early testing for COVID-19 should be considered in hospitalized older adults.

Case Report: Recurrence of Acute Respiratory Distress Syndrome After Bilateral Lung Transplantation.

BACKGROUND: The main causes of early respiratory failure after lung transplantation include primary graft dysfunction (PGD), acute rejection, and infection. This report describes a case of unclear early respiratory failure after bilateral lung transplantation for extensive COVID-19-induced acute respiratory distress syndrome (ARDS). METHODS: We reviewed the patient file to investigate the course of the functional decline and evaluate reasons for early graft failure. Analyzed data included crossmatching results, biopsy results, HLA antibodies testing, bronchoalveolar lavages, respiratory parameters, and medications. RESULTS: After an initial excellent early postoperative course, the patient developed progressive respiratory failure, making re-implantation of extracorporeal membrane oxygenation (ECMO) support necessary. An extensive diagnostic workup revealed no signs of infection or rejection. Because the patient showed no signs of improvement with any treatment, lung-protective ventilation with the intermittent prone position was initiated. The patient's respiratory situation and bilateral opacities slowly improved over the next few weeks, and ECMO support was eventually discontinued. CONCLUSION: With no evidence of PGD, rejection, or infection, recurrent ARDS caused by a systemic immunologic process was seen as the only plausible cause for the patient's respiratory failure after lung transplantation. The fact that ARDS can develop extrapulmonarily, without direct viral or bacterial damage, makes us conclude that the preceding systemic activation and recruitment of immune cells by the primarily injured lung could potentially lead to the recurrence of ARDS even if the injured organ is removed.

Predictors of adverse outcomes in aged patients critically ill with COVID-19: a retrospective study.

Older patients represent an inordinate proportion of intensive care unit (ICU) admissions and ICU mortality associated with coronavirus disease 2019 (COVID-19). In this retrospective cohort study, we examine 198 patients, aged 18 years or older, admitted to the ICU from March to June 2020. We aim to understand the relationships between age, number of comorbidities, and independent living prior to admission on outcomes of mortality, length of stay, renal failure, respiratory failure, and shock. In this cohort, we find that overall mortality was associated with respiratory failure severity (for every decrease of P:F by 50, odds ratio (OR) 2.98 (1.65-6.08)), acute renal failure (OR 4.61 (1.2-19.7)), and age 65 or greater (OR: 3.7 (1.86-7.36)). Surprisingly, increasing age was associated with less severe respiratory failure (R = 0.22, p < 0.01). When adjusting for pre-existing chronic kidney disease, age was not associated with development of acute kidney injury (OR: 1.01 (0.99-1.03)). While chronologic age is associated with mortality, it is not associated independently with severe end organ damage. This is consistent with growing evidence suggesting that a complex interplay between multimorbidity, immunosenescence, and physiologic age is primarily responsible for the vulnerability to COVID-19.

Severe COVID-19 with persistent respiratory failure-A retrospective cohort study in a tertiary centre in Malaysia.

INTRODUCTION: Management of severe COVID-19 patients with persistent respiratory failure after acute phase treatment is not only challenging, but evidence for treatment is scarce, despite some authors reporting favourable clinical responses to corticosteroid therapy in histologically proven secondary organising pneumonia (OP). This study aimed to report the course of the disease, radiological pattern and clinical outcomes of severe COVID-19 patients with persistent respiratory failure. METHODS: This was a retrospective cohort study of severe COVID-19 patients who were admitted to a single tertiary centre from 1 January 2021 to 30 June 2021. The clinical data of the patients during admission and clinic follow-up, including radiological images, were traced using electronic medical records. RESULTS: In our cohort, the mortality rate for those with severe COVID-19 was 23.1% (173/749). Among the survivors, 46.2% (266/576) had persistent respiratory failure (PRF) after 14 days of illness. Of them, 70.3% (187/266) were followed up, and 68% (128/187) received oral corticosteroid (prednisolone) maintenance treatment. OP pattern made up the majority (81%) of the radiological pattern with a mean severity CT score of 10 (SD±3). The mean prednisolone dose was 0.68mg/kg/day with a mean treatment duration of 47 days (SD±18). About one-third of patients (67/187) had respiratory symptoms at 4 weeks (SD±3). Among 78.1% (146/187) who had a repeated CXR during follow-up, only 12 patients (8.2%, SD±3) had radiological improvement of less than 50% at 6 weeks (SD±3), with 2 of them later diagnosed as pulmonary tuberculosis. Functional assessments, such as the 6-minute walk test and the spirometry, were only performed in 52.4% and 15.5% of the patients, respectively. CONCLUSION: Almost half of the patients with severe COVID-19 had PRF, with a predominant radiological OP pattern. More than two-thirds of the PRF patients required prolonged oral corticosteroid treatment. Familiarising clinicians with the disease course, radiological patterns, and potential outcomes of this group of patients may better equip them to manage their patients.

Risk Stratification Based on a Pattern of Immunometabolic Host Factors Is Superior to Body Mass Index-Based Prediction of COVID-19-Associated Respiratory Failure.

Overweight and obesity are associated with chronic low-grade inflammation and represent risk factors for various diseases, including COVID-19. However, most published studies on COVID-19 defined obesity by the body mass index (BMI), which does not encounter adipose tissue distribution, thus neglecting immunometabolic high-risk patterns. Therefore, we comprehensively analyzed baseline anthropometry (BMI, waist-to-height-ratio (WtHR), visceral (VAT), epicardial (EAT), subcutaneous (SAT) adipose tissue masses and liver fat, inflammation markers (CRP, ferritin, interleukin-6), and immunonutritional scores (CRP-to-albumin ratio (CAR), modified Glasgow prognostic score, neutrophile-to-lymphocyte ratio, prognostic nutritional index)) in 58 consecutive COVID-19 patients of the early pandemic phase with regard to the necessity of invasive mechanical ventilation (IMV). Here, metabolically high-risk adipose tissues represented by increased VAT, liver fat, and WtHR strongly correlated with higher levels of inflammation, pathologic immunonutritional scores, and the need for IMV. In contrast, the prognostic value of BMI was inferior and absent with regard to SAT. Multivariable logistic regression analysis identified an optimized IMV risk prediction model employing liver fat, WtHR, and CAR. In summary, we suggest an immunometabolically risk-adjusted model to predict COVID-19-induced respiratory failure better than BMI-based stratification, which warrants prospective validation.

In-hospital mortality of critically Ill patients with interactions of acute kidney injury and acute respiratory failure in the resource-limited settings: Results from SEA-AKI study.

PURPOSE: Our goal was to describe clinical outcomes and explore the physiological interactions between acute kidney injury (AKI) and acute respiratory failure (ARF) in critically ill patients. MATERIALS AND METHODS: Data were retrieved from the SEA-AKI study, a multinational multicenter database of adult ICUs from Thailand, Laos, and Indonesia. AKI was defined using KDIGO criteria stage 2-3. ARF was defined by being mechanically ventilated. Patients were assigned into 6 patterns based on AKI and ARF sequence: "no AKI/ARF", "ARF alone", "AKI alone", "ARF first", "AKI first", and "Concurrent AKI-ARF". The primary outcome was in-hospital mortality of each pattern. RESULTS: A final cohort of 5468 patients were eligible for the analysis. The "Concurrent AKI-ARF" had the highest in-hospital mortality of 69.6%. The "AKI first" and the "ARF first" had in-hospital mortality of 54.4% and 53%, respectively. Among patients with single organ failure, in-hospital mortality was 14.6% and 31.5% in the "AKI alone" and the "ARF alone", accordingly. In-hospital mortality was 12.4% in patients without AKI and ARF. CONCLUSION: Critically ill patients with ARF and AKI are at higher risk of in-hospital death. Different patterns of AKI and ARF interaction result in unique clinical outcomes as well as risk factors.

Inhaled nitric oxide as temporary respiratory stabilization in patients with COVID-19 related respiratory failure (INOCOV): Study protocol for a randomized controlled trial.

BACKGROUND: In March 2020, WHO announced the COVID-19 a pandemic and a major global public health emergency. Mortality from COVID-19 is rapidly increasing globally, with acute respiratory failure as the predominant cause of death. Many patients experience severe hypoxia and life-threatening respiratory failure often requiring mechanical ventilation. To increase safety margins during emergency anaesthesia and rapid sequence intubation (RSI), patients are preoxygenated with a closed facemask with high-flow oxygen and positive end-expiratory pressure (PEEP). Due to the high shunt fraction of deoxygenated blood through the lungs frequently described in COVID-19 however, these measures may be insufficient to avoid harmful hypoxemia. Preoxygenation with inhaled nitric oxide (iNO) potentially reduces the shunt fraction and may thus allow for the necessary margins of safety during RSI. METHODS AND DESIGN: The INOCOV protocol describes a phase II pharmacological trial of inhaled nitric oxide (iNO) as an adjunct to standard of care with medical oxygen in initial airway and ventilation management of patients with known or suspected COVID-19 in acute respiratory failure. The trial is parallel two-arm, randomized, controlled, blinded trial. The primary outcome measure is the change in oxygen saturation (SpO2), and the null hypothesis is that there is no difference in the change in SpO2 following initiation of iNO. TRIAL REGISTRATION: EudraCT number 2020-001656-18; WHO UTN: U1111-1250-1698. Protocol version: 2.0 (June 25th, 2021).

Pneumocystis pneumonia with respiratory failure in a HIV-negative patient following short course of low-dose to moderate-dose prednisolone for a dermatological condition.

A woman in her 80s was admitted with 5 days of progressive dyspnoea and hypoxic respiratory failure, in the setting of receiving a 3-week course of low-dose to moderate-dose prednisolone for a pruritic skin rash. Her medical history was not significant for major medical comorbidities or any other clear risk factors for secondary immunosuppression apart from advanced age. CT revealed widespread small-airway and parenchymal disease with ground-glass opacities consistent with atypical respiratory infection. Sputum PCR confirmed Pneumocystis jirovecii She was diagnosed with Pneumocystis jirovecii pneumonia (PJP) in the context of her clinical presentation, radiological features and PCR result. Her HIV status was negative. The patient was treated with 4 weeks of trimethoprim-sulfamethoxazole and 3 weeks of adjunctive prednisolone. She initially required high-dependency unit support with non-invasive ventilation. In this case report, we review the literature regarding PJP in the dermatology setting.

Acute neuromuscular syndromes with respiratory failure during COVID-19 pandemic: Where we stand and challenges ahead.

Coronavirus disease 2019 (COVID-19), a disease caused by the novel betacoronavirus SARS-COV-2, has become a global pandemic threat. SARS- COV-2 is structurally similar to SARS-COV, and both bind to the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. While patients typically present with fever, shortness of breath, sore throat, and cough, in some cases neurologic manifestations occur due to both direct and indirect involvement of the nervous system. Case reports include anosmia, ageusia, central respiratory failure, stroke, acute necrotizing hemorrhagic encephalopathy, toxic-metabolic encephalopathy, headache, myalgia, myelitis, ataxia, and various neuropsychiatric manifestations. Some patients with COVID-19 may present with concurrent acute neuromuscular syndromes such as myasthenic crisis (MC), Guillain-Barré syndrome (GBS) and idiopathic inflammatory myopathies (IIM); these conditions coupled with respiratory failure could trigger a life-threatening condition. Here, we review the current state of knowledge on acute neuromuscular syndromes with respiratory failure related to COVID-19 infection in an attempt to clarify and to manage the muscle dysfunction overlapping SARS-COV-2 infection.

Silent hypoxia is not an identifiable characteristic in patients with COVID-19 infection.

BACKGROUND: We aimed to assess whether asymptomatic ("happy") hypoxia was an identifiable physiological phenotype of COVID-19 acute respiratory distress syndrome (ARDS), and associated with need for ICU admission. METHODS: We performed an observational cohort study of all adult patients admitted with hypoxaemic respiratory failure to a large acute hospital Trust serving the East Midlands, UK. Patients with confirmed COVID-19 were compared to those without. Physiological response to hypoxaemia was modelled using a linear mixed effects model. RESULTS: Of 1,586 patients included, 75% tested positive for SARS-CoV-2. The ROX index was 2.08 min-1 lower (1.56-2.61, p < 0.001) in the COVID-19 cohort when adjusted for age and ethnicity, suggesting an enhanced respiratory response to hypoxia compared to the non-Covid-19 patients. There was substantial residual inter- and intra-patient variability in the respiratory response to hypoxaemia. 33% of the infected cohort required ICU, and of these 31% died within 60 days. ICU admission and mortality were both associated with an enhanced respiratory response for all degrees of hypoxaemia. CONCLUSIONS: Patients with COVID-19 display a more symptomatic phenotype in response to hypoxaemia than those with other causes of hypoxaemic respiratory failure, however individual patients exhibit a wide range of responses. As such although asymptomatic hypoxaemia may be a phenomenon in any individual patient with hypoxaemic respiratory failure, it is no more frequently observed in those with SARS-CoV-2 infection than without.

Factors for success of awake prone positioning in patients with COVID-19-induced acute hypoxemic respiratory failure: analysis of a randomized controlled trial.

BACKGROUND: Awake prone positioning (APP) improves oxygenation in coronavirus disease (COVID-19) patients and, when successful, may decrease the risk of intubation. However, factors associated with APP success remain unknown. In this secondary analysis, we aimed to assess whether APP can reduce intubation rate in patients with COVID-19 and to focus on the factors associated with success. METHODS: In this multicenter randomized controlled trial, conducted in three high-acuity units, we randomly assigned patients with COVID-19-induced acute hypoxemic respiratory failure (AHRF) requiring high-flow nasal cannula (HFNC) oxygen to APP or standard care. Primary outcome was intubation rate at 28 days. Multivariate analyses were performed to identify the predictors associated to treatment success (survival without intubation). RESULTS: Among 430 patients randomized, 216 were assigned to APP and 214 to standard care. The APP group had a lower intubation rate (30% vs 43%, relative risk [RR] 0.70; CI95 0.54-0.90, P = 0.006) and shorter hospital length of stay (11 interquartile range [IQR, 9-14] vs 13 [IQR, 10-17] days, P = 0.001). A respiratory rate ≤ 25 bpm at enrollment, an increase in ROX index > 1.25 after first APP session, APP duration > 8 h/day, and a decrease in lung ultrasound score ≥ 2 within the first 3 days were significantly associated with treatment success for APP. CONCLUSION: In patients with COVID-19-induced AHRF treated by HFNC, APP reduced intubation rate and improved treatment success. A longer APP duration is associated with APP success, while the increase in ROX index and decrease in lung ultrasound score after APP can also help identify patients most likely to benefit. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov at July 20, 2021. Identification number NCT04477655. https://clinicaltrials.gov/ct2/show/NCT04477655?term=PRO-CARF&draw=2&rank=1.

Risk Factors for Severe COVID-19 Outcomes Among Persons Aged ≥18 Years Who Completed a Primary COVID-19 Vaccination Series - 465 Health Care Facilities, United States, December 2020-October 2021.

Vaccination against SARS-CoV-2, the virus that causes COVID-19, is highly effective at preventing COVID-19-associated hospitalization and death; however, some vaccinated persons might develop COVID-19 with severe outcomes† (1,2). Using data from 465 facilities in a large U.S. health care database, this study assessed the frequency of and risk factors for developing a severe COVID-19 outcome after completing a primary COVID-19 vaccination series (primary vaccination), defined as receipt of 2 doses of an mRNA vaccine (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) or a single dose of JNJ-78436735 [Janssen (Johnson & Johnson)] ≥14 days before illness onset. Severe COVID-19 outcomes were defined as hospitalization with a diagnosis of acute respiratory failure, need for noninvasive ventilation (NIV), admission to an intensive care unit (ICU) including all persons requiring invasive mechanical ventilation, or death (including discharge to hospice). Among 1,228,664 persons who completed primary vaccination during December 2020-October 2021, a total of 2,246 (18.0 per 10,000 vaccinated persons) developed COVID-19 and 189 (1.5 per 10,000) had a severe outcome, including 36 who died (0.3 deaths per 10,000). Risk for severe outcomes was higher among persons who were aged ≥65 years, were immunosuppressed, or had at least one of six other underlying conditions. All persons with severe outcomes had at least one of these risk factors, and 77.8% of those who died had four or more risk factors. Severe COVID-19 outcomes after primary vaccination are rare; however, vaccinated persons who are aged ≥65 years, are immunosuppressed, or have other underlying conditions might be at increased risk. These persons should receive targeted interventions including chronic disease management, precautions to reduce exposure, additional primary and booster vaccine doses, and effective pharmaceutical therapy as indicated to reduce risk for severe COVID-19 outcomes. Increasing COVID-19 vaccination coverage is a public health priority.

Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers.

BACKGROUND: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. METHODS: Plasma levels of sex hormones (testosterone and 17ß-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. RESULTS: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. CONCLUSIONS: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring.

Circulating levels of calprotectin, a signature of neutrophil activation in prediction of severe respiratory failure in COVID-19 patients: a multicenter, prospective study (CalCov study).

OBJECTIVE: Severe COVID-19 is characterized by a dysregulated immune response in which neutrophils play a critical role. Calprotectin reflects neutrophil activation and is involved in the self-amplifying thrombo-inflammatory storm in severe COVID-19. We aimed to evaluate the role of calprotectin in early prediction of severity in COVID-19 patients. METHODS: This was a multicenter prospective observational study enrolling consecutive adult COVID-19 patients. On arrival to emergency department, blood samples were collected for laboratory tests, including serum calprotectin. The primary outcome was severe respiratory failure requiring invasive mechanical ventilation and the secondary outcome was need for Intensive Care Unit (ICU) admission. RESULTS: Study population included 395 patients, 57 (14.4%) required invasive mechanical ventilation and 100 (25.3%) were admitted to ICU. Median serum calprotectin levels were significantly higher in intubated (3.73 mg/L vs. 2.63 mg/L; p < 0.001) and ICU patients (3.48 mg/L vs. 2.60 mg/L; p = 0.001). Calprotectin showed a significant accuracy to predict the need for invasive mechanical ventilation (ROC AUC 0.723) and ICU admission (ROC AUC 0.650). In multivariate analysis, serum calprotectin was an independent predictor of invasive mechanical ventilation (OR 1.161) and ICU admission (OR 1.068). CONCLUSION: Serum calprotectin can be used as an early predictor of severity in COVID-19 patients.

The timing of intubation and principles of ICU care in COVID-19

Coronavirus disease-19 (COVID-19) has been a serious health problem since it was first identified in Wuhan, China, in December 2019 and has created a global crisis with its economic, sociological, and psychological aspects. Approximately 15% of cases have a severe clinical presentation, and 5% of patients require admission to the intensive care unit. A significant proportion of patients presents with a rapidly progressing acute respiratory failure and require invasive mechanical ventilation. This article aimed to evaluate how the optimal intubation timing should be determined in cases of acute respiratory failure due to COVID-19 and to offer recommendations for basic intensive care support in the light of our current knowledge.

Cerebrospinal fluid and serum interleukins 6 and 8 during the acute and recovery phase in COVID-19 neuropathy patients.

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.

Peptides: Prospects for Use in the Treatment of COVID-19.

There is a vast practice of using antimalarial drugs, RAS inhibitors, serine protease inhibitors, inhibitors of the RNA-dependent RNA polymerase of the virus and immunosuppressants for the treatment of the severe form of COVID-19, which often occurs in patients with chronic diseases and older persons. Currently, the clinical efficacy of these drugs for COVID-19 has not been proven yet. Side effects of antimalarial drugs can worsen the condition of patients and increase the likelihood of death. Peptides, given their physiological mechanism of action, have virtually no side effects. Many of them are geroprotectors and can be used in patients with chronic diseases. Peptides may be able to prevent the development of the pathological process during COVID-19 by inhibiting SARS-CoV-2 virus proteins, thereby having immuno- and bronchoprotective effects on lung cells, and normalizing the state of the hemostasis system. Immunomodulators (RKDVY, EW, KE, AEDG), possessing a physiological mechanism of action at low concentrations, appear to be the most promising group among the peptides. They normalize the cytokines' synthesis and have an anti-inflammatory effect, thereby preventing the development of disseminated intravascular coagulation, acute respiratory distress syndrome and multiple organ failure.