COVID-19 treatment: a growing (anti)body of evidence

South African General Practitioner ◽

10.36303/sagp.2020.1.5.0048 ◽

2020 ◽

pp. 172-174

Author(s):

K Outhoff

Keyword(s):

Mechanical Ventilation ◽

Lower Respiratory Tract ◽

Standard Care ◽

Treatment Options ◽

Invasive Mechanical Ventilation ◽

Collaborative Group ◽

Severe Illness ◽

Adults And Children ◽

Tract Involvement ◽

Anti Body

Our lives changed dramatically eight months ago when we went into a hard nationwide lockdown in a bid to limit the transmission of our new spiky foe, SARS-CoV-2. We endured the uncertainties of autumn, and then the winter and the cold July COVID-19 peak. At this time, Oxford University’s RECOVERY Collaborative group first reported on dexamethasone (6 mg daily for 10 days) significantly lowering the 28-day mortality in hospitalised COVID-19 patients on invasive mechanical ventilation or on oxygen alone, by as much as a third and a fifth, respectively. It was hypothesised that glucocorticoids modulate inflammation-mediated lung injury, thus reducing the likely progression to respiratory failure and death in patients with severe illness. This made us perk up because a couple of months earlier, the intravenous antiviral, remdesivir (100 mg), also administered for 10 days, had shown promise in shortening the time to recovery by a median of five days compared to placebo, but not in reducing death in hospitalised COVID-19 patients with lower respiratory tract involvement. The FDA granted remdesivir Emergency Use Authorization (EUA) in May for the treatment of adults and children hospitalised with suspected or laboratory-confirmed COVID-19 based on this meagre evidence, as there were no other treatment options at the time. Meanwhile, dexamethasone, which is relatively cheap, quickly became the standard care in patients requiring oxygen.

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Multicenter Interim Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piaa115 ◽

2020 ◽

Cited By ~ 3

Author(s):

Kathleen Chiotos ◽

Molly Hayes ◽

David W Kimberlin ◽

Sarah B Jones ◽

Scott H James ◽

...

Keyword(s):

Mechanical Ventilation ◽

Pediatric Patients ◽

Invasive Mechanical Ventilation ◽

Great Majority ◽

Supplemental Oxygen ◽

Critically Ill Children ◽

Severe Illness ◽

Noninvasive Mechanical Ventilation ◽

Oxygen Requirement ◽

Web Based

Abstract Background Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children. Methods A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion. Results Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children. Conclusions Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.

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An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients

Scientific Reports ◽

10.1038/s41598-021-88509-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Álvaro Réa-Neto ◽

Rafaella Stradiotto Bernardelli ◽

Bruna Martins Dzivielevski Câmara ◽

Fernanda Baeumle Reese ◽

Marcos Vinicius Oliveira Queiroga ◽

...

Keyword(s):

Mechanical Ventilation ◽

Renal Dysfunction ◽

Standard Care ◽

Clinical Status ◽

Invasive Mechanical Ventilation ◽

Intervention Group ◽

Phase Iii ◽

Ordinal Scale ◽

Open Label ◽

Once Daily

AbstractDespite several studies designed to evaluate the efficacy of chloroquine and hydroxychloroquine in the treatment of coronavirus disease 2019 (COVID-19), there is still doubt about the effects of these drugs, especially in patients with severe forms of the disease. This randomized, open-label, controlled, phase III trial assessed the efficacy of chloroquine or hydroxychloroquine for five days in combination with standard care compared to standard care alone in patients hospitalized with severe COVID-19. Chloroquine 450 mg BID on day 1 and 450 mg once daily from days 2 to 5 or hydroxychloroquine 400 mg BID on day 1 and 400 mg once daily from days 2 to 5 were administered in the intervention group. Patients were enrolled from April 16 to August 06, 2020, in 6 hospitals in southern Brazil. The primary outcome was the clinical status measured on day 14 after randomization with a 9-point ordinal scale. The main secondary outcomes were all-cause mortality; invasive mechanical ventilation use; the incidence of acute renal dysfunction in 28 days; and the clinical status of patients on days 5, 7, 10 and 28. All patients with a positive RT-PCR result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were analyzed (modified intention to treat (mITT) population). Arrythmias and cardiovascular complications were assessed as safety outcomes. A total of 105 patients were enrolled and followed for 28 days. The trial was stopped before reaching the planned sample size due to harmful effects. Patients in the intervention group had a worse clinical outcome on the 14th day (odds ratio (OR) 2.45 [1.17 to 4.93], p = 0.016) and on the 28th day (OR 2.47 [1.15 to 5.30], p = 0.020). Moreover, the intervention group had higher incidences of invasive mechanical ventilation use (risk ratio (RR) 2.15 [1.05 to 4.40], p = 0.030) and severe renal dysfunction (KDIGO stage 3) (RR 2.24 [1.01 to 4.99], p = 0.042) until the 28th day of follow-up. No significant arrythmia was noted. In patients with severe COVID-19, the use of chloroquine/hydroxychloroquine added to standard treatment resulted in a significant worsening of clinical status, an increased risk of renal dysfunction and an increased need for invasive mechanical ventilation.Trial Registration: ClinicalTrials.gov, NCT04420247. Registered 09 June 2020—Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/study/NCT04420247.

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Highlights from the Respiratory Failure and Mechanical Ventilation 2020 Conference

ERJ Open Research ◽

10.1183/23120541.00752-2020 ◽

2021 ◽

Vol 7 (1) ◽

pp. 00752-2020

Author(s):

Adelaide Withers ◽

Tiffany Choi Ching Man ◽

Rebecca D'Cruz ◽

Heder de Vries ◽

Christoph Fisser ◽

...

Keyword(s):

Mechanical Ventilation ◽

Intensive Care ◽

Respiratory Failure ◽

Patient Selection ◽

Treatment Options ◽

Early Career ◽

European Respiratory Society ◽

Diagnostic Strategies ◽

Adults And Children ◽

International Experts

The Respiratory Intensive Care Assembly of the European Respiratory Society organised the first Respiratory Failure and Mechanical Ventilation Conference in Berlin in February 2020. The conference covered acute and chronic respiratory failure in both adults and children. During this 3-day conference, patient selection, diagnostic strategies and treatment options were discussed by international experts. Lectures delivered during the event have been summarised by Early Career Members of the Assembly and take-home messages highlighted.

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Outcomes and characteristics of COVID-19 patients treated with CPAP/ HFNO outside of the intensive care setting

ERJ Open Research ◽

10.1183/23120541.00318-2021 ◽

2021 ◽

pp. 00318-2021

Author(s):

Dominic L Sykes ◽

Michael G Crooks ◽

Khaing Thu Thu ◽

Oliver I Brown ◽

Theodore J p Tyrer ◽

...

Keyword(s):

Mechanical Ventilation ◽

Intensive Care ◽

Respiratory Failure ◽

Care Setting ◽

Treatment Options ◽

Invasive Mechanical Ventilation ◽

Respiratory Support ◽

Intensive Care Setting ◽

Non Invasive ◽

Significant Difference

BackgroundContinuous Positive Airway Pressure (CPAP) and High Flow Nasal Oxygen (HFNO) have been used to manage hypoxaemic respiratory failure secondary to COVID-19 pneumonia. Limited data are available for patients treated with non-invasive respiratory support outside of the intensive care setting.MethodsIn this single-centre observational study we observed the characteristics, physiological observations, laboratory tests, and outcomes of all consecutive patients with COVID-19 pneumonia between April 2020 and March 2021 treated with non-invasive respiratory support outside of the intensive care setting.ResultsWe report the outcomes of 140 patients (Mean Age=71.2 [sd=11.1], 65% Male [n=91]) treated with CPAP/HFNO outside of the intensive care setting. Overall mortality was 59% and was higher in those deemed unsuitable for mechanical ventilation (72%). The mean age of survivors was significantly lower than those who died (66.1 versus 74.4 years, p<0.001). Those who survived their admission also had a significantly lower median Clinical Frailty Score than the non-survivor group (2 versus 4, p<0.001). We report no significant difference in mortality between those treated with CPAP (n=92, mortality: 60%) or HFNO (n=48, mortality: 56%). Treatment was well tolerated in 86% of patients receiving either CPAP or HFNO.ConclusionsCPAP and HFNO delivered outside of the intensive care setting are viable treatment options for patients with hypoxaemic respiratory failure secondary to COVID-19 pneumonia, including those considered unsuitable for invasive mechanical ventilation. This provides an opportunity to safeguard intensive care capacity for COVID-19 patients requiring invasive mechanical ventilation.

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Diaphragmatic palsy after cardiac surgery in adult and pediatric patients

Asian Cardiovascular and Thoracic Annals ◽

10.1177/0218492319859806 ◽

2019 ◽

Vol 27 (6) ◽

pp. 481-485 ◽

Cited By ~ 2

Author(s):

Khalid Ebrahim Al-Ebrahim ◽

Ahmed Abdelrahman Elassal ◽

Osama Saber Eldib ◽

Ahmed Hassan Abdelsalam Abdalla ◽

Amr Ragab Abdelaty Allam ◽

...

Keyword(s):

Mechanical Ventilation ◽

Cardiac Surgery ◽

Pediatric Patients ◽

Treatment Options ◽

Diaphragmatic Paralysis ◽

Low Cardiac Output ◽

Diaphragmatic Palsy ◽

Median Period ◽

Adults And Children ◽

One Year

Background Important differences in the mechanism of respiration between adults and children warrant distinction in the management of diaphragmatic paralysis as a complication of cardiac surgery. We describe the management and outcomes of this complication in both groups. Methods We retrospectively analyzed 16 patients (5 adults and 11 children) with diaphragmatic paralysis after cardiac surgery performed between 2008 and 2018. Clinical examination, chest radiography, and confirmation with fluoroscopy in selected cases were our modalities of diagnosis. All adults were managed conservatively, whereas plication was performed in all children. Results The incidence of diaphragmatic paralysis was 0.98% in pediatric patients and 0.43% in adults. The mean age was 2.33 ± 2.59 years in children and 53.2 ± 17.99 years in adults. All adults were symptomatic. All children showed difficulty in weaning from mechanical ventilation after cardiac surgery. The period of mechanical ventilation before plication was 2–6 days (median 4 days). Death occurred as a result of low cardiac output in a 10-year-old boy, and due to respiratory failure in a 30-year-old woman. Children were successfully weaned from mechanical ventilation after diaphragmatic plication. The median time to extubation after plication was 2.5 days (range 1–13 days). The median period of recovery in adults was 52 days (range 32–85 days). All survivors had acceptable outcomes at 6 months to one year. Conclusion Conservative management in adults and early plication in children are viable treatment options for diaphragmatic palsy after cardiac surgery, with acceptable outcomes.

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Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19)

Clinical Infectious Diseases ◽

10.1093/cid/ciaa351 ◽

2020 ◽

Vol 71 (15) ◽

pp. 799-806 ◽

Cited By ~ 104

Author(s):

Kaijin Xu ◽

Yanfei Chen ◽

Jing Yuan ◽

Ping Yi ◽

Cheng Ding ◽

...

Keyword(s):

Risk Factors ◽

Mechanical Ventilation ◽

Hospital Admission ◽

Invasive Mechanical Ventilation ◽

Corticosteroid Treatment ◽

Viral Rna ◽

Severe Illness ◽

Illness Onset ◽

Factors Associated ◽

Male Sex

Abstract Background An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. Methods In this retrospective study, risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from 2 hospitals outside Wuhan. Results The median (interquartile range) duration of SARS-CoV-2 RNA detection was 17 (13–22) days as measured from illness onset. When comparing patients with early (<15 days) and late (≥15 days after illness onset) viral RNA clearance, prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006), and corticosteroid treatment (P = .025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (P < .001) and focal absorption on radiograph images (P < .001) than patients with early SARS-CoV-2 RNA clearance. Male sex (OR, 3.24; 95% CI, 1.31–8.02), delayed hospital admission (OR, 1.30; 95% CI, 1.10–1.54), and invasive mechanical ventilation (OR, 9.88; 95% CI, 1.11–88.02) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. Conclusions Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients.

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Predictors at admission of mechanical ventilation and death in an observational cohort of adults hospitalized with COVID-19

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1459 ◽

2020 ◽

Author(s):

Brendan R Jackson ◽

Jeremy A W Gold ◽

Pavithra Natarajan ◽

John Rossow ◽

Robyn Neblett Fanfair ◽

...

Keyword(s):

Coronary Artery Disease ◽

Mechanical Ventilation ◽

Coronary Artery ◽

Invasive Mechanical Ventilation ◽

Vital Signs ◽

Severe Illness ◽

Antihypertensive Medications ◽

Radiographic Findings ◽

Observational Cohort ◽

Artery Disease

Abstract Background Coronavirus disease (COVID-19) can cause severe illness and death. Predictors of poor outcome collected on hospital admission may inform clinical and public health decisions. Methods We conducted a retrospective observational cohort investigation of 297 adults admitted to eight academic and community hospitals in Georgia, United States, during March 2020. Using standardized medical record abstraction, we collected data on predictors including admission demographics, underlying medical conditions, outpatient antihypertensive medications, recorded symptoms, vital signs, radiographic findings, and laboratory values. We used random forest models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CI) for predictors of invasive mechanical ventilation (IMV) and death. Results Compared with age <45 years, ages 65–74 years and ≥75 years were predictors of IMV (aOR 3.12, CI 1.47–6.60; aOR 2.79, CI 1.23–6.33) and the strongest predictors for death (aOR 12.92, CI 3.26–51.25; aOR 18.06, CI 4.43–73.63). Comorbidities associated with death (aORs from 2.4 to 3.8, p <0.05) included end-stage renal disease, coronary artery disease, and neurologic disorders, but not pulmonary disease, immunocompromise, or hypertension. Pre-hospital use vs. non-use of angiotensin receptor blockers (aOR 2.02, CI 1.03–3.96) and dihydropyridine calcium channel blockers (aOR 1.91, CI 1.03–3.55) were associated with death. Conclusions After adjustment for patient and clinical characteristics, older age was the strongest predictor of death, exceeding comorbidities, abnormal vital signs, and laboratory test abnormalities. That coronary artery disease, but not chronic lung disease, was associated with death among hospitalized patients warrants further investigation, as do associations between certain antihypertensive medications and death.

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Value of Chest Radiographic Pattern in RSV Disease of the Newborn: A Multicenter Retrospective Cohort Study

Critical Care Research and Practice ◽

10.1155/2012/861867 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Américo Gonçalves ◽

Gustavo Rocha ◽

Hercília Guimarães ◽

Paula Cristina Fernandes ◽

Elisa Proença ◽

...

Keyword(s):

Mechanical Ventilation ◽

Cohort Study ◽

Respiratory Tract ◽

Chest Radiograph ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Lower Respiratory Tract ◽

Invasive Mechanical Ventilation ◽

Supplemental Oxygen ◽

Preterm Neonates

Respiratory syncytial virus (RSV) lower respiratory tract infection is the most common viral respiratory infection in infants. Several authors have sought to determine which risk factors are the best predictors for severe RSV disease. Our aim was to evaluate if a specific chest radiographic pattern in RSV disease can predict the disease severity. We conducted a multicenter retrospective cohort study in term and preterm neonates with confirmed lower respiratory tract RSV infection, admitted to neonatal intensive care units (NICU) from 2000 to 2010. To determine which factors independently predicted the outcomes, multivariate logistic regression analysis was performed. A total of 259 term and preterm neonates were enrolled. Patients with a consolidation pattern on the chest radiograph at admission (n=101) had greater need for invasive mechanical ventilation (OR: 2.5;P=.015), respiratory support (OR: 2.3;P=.005), supplemental oxygen (OR: 3.0;P=.008), and prolonged stay in the NICU (>7 days) (OR: 1.8;P=.025). Newborns with a consolidation pattern on admission chest radiograph had a more severe disease course, with greater risk of invasive mechanical ventilation, respiratory support, supplemental oxygen, and prolonged hospitalization.

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