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Pragmatic Recommendations for Therapeutics of Hospitalized COVID-19 Patients in Low- and Middle-Income Countries.

ABSTRACT: The therapeutic options for COVID-19 patients are currently limited, but numerous randomized controlled trials are being completed, and many are on the way. For COVID-19 patients in low- and middle-income countries (LMICs), we recommend against using remdesivir outside of a clinical trial. We recommend against using hydroxychloroquine ± azithromycin or lopinavir-ritonavir. We suggest empiric antimicrobial treatment for likely coinfecting pathogens if an alternative infectious cause is likely. We suggest close monitoring without additional empiric antimicrobials if there are no clinical or laboratory signs of other infections. We recommend using oral or intravenous low-dose dexamethasone in adults with COVID-19 disease who require oxygen or mechanical ventilation. We recommend against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen. We recommend using alternate equivalent doses of steroids in the event that dexamethasone is unavailable. We also recommend using low-dose corticosteroids in patients with refractory shock requiring vasopressor support. We recommend against the use of convalescent plasma and interleukin-6 inhibitors, such as tocilizumab, for the treatment of COVID-19 in LMICs outside of clinical trials.

SUBMITTER: Shetty VU

PROVIDER: S-EPMC7957231 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Pragmatic Recommendations for Therapeutics of Hospitalized COVID-19 Patients in Low- and Middle-Income Countries.

Shetty Varun U VU Brotherton Brian Jason BJ Achilleos Andrew A Akrami Kevan M KM Barros Lia M LM Checkley William W Cobb Natalie N Maximous Stephanie S Misango David D Park Casey C Taran Shaurya S Lee Burton W BW

The American journal of tropical medicine and hygiene 20201229 3_Suppl

The therapeutic options for COVID-19 patients are currently limited, but numerous randomized controlled trials are being completed, and many are on the way. For COVID-19 patients in low- and middle-income countries (LMICs), we recommend against using remdesivir outside of a clinical trial. We recommend against using hydroxychloroquine ± azithromycin or lopinavir-ritonavir. We suggest empiric antimicrobial treatment for likely coinfecting pathogens if an alternative infectious cause is likely. We ...[more]

PMID: 33377451

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Project description:Effective identification and prognostication of severe COVID-19 patients presenting to healthcare facilities are essential to reducing morbidity and mortality. Low- and middle-income country (LMIC) facilities often suffer from restrictions in availability of human resources, laboratory testing, medications, and imaging during routine functioning, and such shortages may worsen during times of surge. Low- and middle-income country healthcare providers will need contextually appropriate tools to identify and triage potential COVID-19 patients. We report on a series of LMIC-appropriate recommendations and suggestions for screening and triage of COVID-19 patients in LMICs, based on a pragmatic, experience-based appraisal of existing literature. We recommend that all patients be screened upon first contact with the healthcare system using a locally approved questionnaire to identify individuals who have suspected or confirmed COVID-19. We suggest that primary screening tools used to identify individuals who have suspected or confirmed COVID-19 include a broad range of signs and symptoms based on standard case definitions of COVID-19 disease. We recommend that screening include endemic febrile illness per routine protocols upon presentation to a healthcare facility. We recommend that, following screening and implementation of appropriate universal source control measures, suspected COVID-19 patients be triaged with a triage tool appropriate for the setting. We recommend a standardized severity score based on the WHO COVID-19 disease definitions be assigned to all suspected and confirmed COVID-19 patients before their disposition from the emergency unit. We suggest against using diagnostic imaging to improve triage of reverse transcriptase (RT)-PCR-confirmed COVID-19 patients, unless a patient has worsening respiratory status. We suggest against the use of point-of-care lung ultrasound to improve triage of RT-PCR-confirmed COVID-19 patients. We suggest the use of diagnostic imaging to improve sensitivity of appropriate triage in suspected COVID-19 patients who are RT-PCR negative but have moderate to severe symptoms and are suspected of a false-negative RT-PCR with high risk of disease progression. We suggest the use of diagnostic imaging to improve sensitivity of appropriate triage in suspected COVID-19 patients with moderate or severe clinical features who are without access to RT-PCR testing for SARS-CoV-2.

Project description:New studies of COVID-19 are constantly updating best practices in clinical care. Often, it is impractical to apply recommendations based on high-income country investigations to resource limited settings in low- and middle-income countries (LMICs). We present a set of pragmatic recommendations for the management of anticoagulation and thrombotic disease for hospitalized patients with COVID-19 in LMICs. In the absence of contraindications, we recommend prophylactic anticoagulation with either low molecular weight heparin (LMWH) or unfractionated heparin (UFH) for all hospitalized COVID-19 patients in LMICs. If available, we recommend LMWH over UFH for venous thromboembolism (VTE) prophylaxis to minimize risk to healthcare workers. We recommend against the use of aspirin for VTE prophylaxis in hospitalized COVID-19 and non-COVID-19 patients in LMICs. Because of limited evidence, we suggest against the use of "enhanced" or "intermediate" prophylaxis in COVID-19 patients in LMICs. Based on current available evidence, we recommend against the initiation of empiric therapeutic anticoagulation without clinical suspicion for VTE. If contraindications exist to chemical prophylaxis, we recommend mechanical prophylaxis with intermittent pneumatic compression (IPC) devices or graduated compression stockings (GCS) for hospitalized COVID-19 patients in LMICs. In LMICs, we recommend initiating therapeutic anticoagulation for hospitalized COVID-19 patients, in accordance with local clinical practice guidelines, if there is high clinical suspicion for VTE, even in the absence of testing. If available, we recommend LMWH over UFH or Direct oral anticoagulants for treatment of VTE in LMICs to minimize risk to healthcare workers. In LMIC settings where continuous intravenous UFH or LMWH are unavailable or not feasible to use, we recommend fixed dose heparin, adjusted to body weight, in hospitalized COVID-19 patients with high clinical suspicion of VTE. We suggest D-dimer measurement, if available and affordable, at the time of admission for risk stratification, or when clinical suspicion for VTE is high. For hospitalized COVID-19 patients in LMICs, based on current available evidence, we make no recommendation on the use of serial D-dimer monitoring for the initiation of therapeutic anticoagulation. For hospitalized COVID-19 patients in LMICs receiving intravenous therapeutic UFH, we recommend serial monitoring of partial thromboplastin time or anti-factor Xa level, based on local laboratory capabilities. For hospitalized COVID-19 patients in LMICs receiving LMWH, we suggest against serial monitoring of anti-factor Xa level. We suggest serial monitoring of platelet counts in patients receiving therapeutic anticoagulation for VTE, to assess risk of bleeding or development of heparin induced thrombocytopenia.

Project description:Management of patients with severe or critical COVID-19 is mainly modeled after care of patients with severe pneumonia or acute respiratory distress syndrome from other causes. These models are based on evidence that primarily originates from investigations in high-income countries, but it may be impractical to apply these recommendations to resource-restricted settings in low- and middle-income countries (LMICs). We report on a set of pragmatic recommendations for microbiology and laboratory testing, imaging, and the use of diagnostic and prognostic models in patients with severe COVID-19 in LMICs. For diagnostic testing, where reverse transcription-PCR (RT-PCR) testing is available and affordable, we recommend using RT-PCR of the upper or lower respiratory specimens and suggest using lower respiratory samples for patients suspected of having COVID-19 but have negative RT-PCR results for upper respiratory tract samples. We recommend that a positive RT-PCR from any anatomical source be considered confirmatory for SARS-CoV-2 infection, but, because false-negative testing can occur, recommend that a negative RT-PCR does not definitively rule out active infection if the patient has high suspicion for COVID-19. We suggest against using serologic assays for the detection of active or past SARS-CoV-2 infection, until there is better evidence for its usefulness. Where available, we recommend the use of point-of-care antigen-detecting rapid diagnostic testing for SARS-CoV-2 infection as an alternative to RT-PCR, only if strict quality control measures are guaranteed. For laboratory testing, we recommend a baseline white blood cell differential platelet count and hemoglobin, creatinine, and liver function tests and suggest a baseline C-reactive protein, lactate dehydrogenase, troponin, prothrombin time (or other coagulation test), and D-dimer, where such testing capabilities are available. For imaging, where availability of standard thoracic imaging is limited, we suggest using lung ultrasound to identify patients with possible COVID-19, but recommend against its use to exclude COVID-19. We suggest using lung ultrasound in combination with clinical parameters to monitor progress of the disease and responses to therapy in COVID-19 patients. We currently suggest against using diagnostic and prognostic models as these models require extensive laboratory testing and imaging, which often are limited in LMICs.

Project description:Management of patients with severe or critical COVID-19 is mainly modeled after care for patients with severe pneumonia or acute respiratory distress syndrome (ARDS) from other causes, and these recommendations are based on evidence that often originates from investigations in resource-rich intensive care units located in high-income countries. Often, it is impractical to apply these recommendations to resource-restricted settings, particularly in low- and middle-income countries (LMICs). We report on a set of pragmatic recommendations for acute respiratory failure and mechanical ventilation management in patients with severe/critical COVID-19 in LMICs. We suggest starting supplementary oxygen when SpO2 is persistently lower than 94%. We recommend supplemental oxygen to keep SpO2 at 88-95% and suggest higher targets in settings where continuous pulse oximetry is not available but intermittent pulse oximetry is. We suggest a trial of awake prone positioning in patients who remain hypoxemic; however, this requires close monitoring, and clear failure and escalation criteria. In places with an adequate number and trained staff, the strategy seems safe. We recommend to intubate based on signs of respiratory distress more than on refractory hypoxemia alone, and we recommend close monitoring for respiratory worsening and early intubation if worsening occurs. We recommend low-tidal volume ventilation combined with FiO2 and positive end-expiratory pressure (PEEP) management based on a high FiO2/low PEEP table. We recommend against using routine recruitment maneuvers, unless as a rescue therapy in refractory hypoxemia, and we recommend using prone positioning for 12-16 hours in case of refractory hypoxemia (PaO2/FiO2 < 150 mmHg, FiO2 ≥ 0.6 and PEEP ≥ 10 cmH2O) in intubated patients as standard in ARDS patients. We also recommend against sharing one ventilator for multiple patients. We recommend daily assessments for readiness for weaning by a low-level pressure support and recommend against using a T-piece trial because of aerosolization risk.

Project description:BackgroundCOVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HICs).ObjectivesThe main aims were to compare the frequency of coagulopathy complications in developing countries (low- and middle-income countries [LMICs]) with those in HICs, delineate the frequency across a range of treatment levels, and determine associations with in-hospital mortality.MethodsAdult patients enrolled in an observational, multinational registry, the International Severe Acute Respiratory and Emerging Infections COVID-19 study, between January 1, 2020, and September 15, 2021, met inclusion criteria, including admission to a hospital for laboratory-confirmed, acute COVID-19 and data on complications and survival. The advanced-treatment cohort received care, such as admission to the intensive care unit, mechanical ventilation, or inotropes or vasopressors; the basic-treatment cohort did not receive any of these interventions.ResultsThe study population included 495,682 patients from 52 countries, with 63% from LMICs and 85% in the basic treatment cohort. The frequency of coagulopathy complications was higher in HICs (0.76%-3.4%) than in LMICs (0.09%-1.22%). Complications were more frequent in the advanced-treatment cohort than in the basic-treatment cohort. Coagulopathy complications were associated with increased in-hospital mortality (odds ratio, 1.58; 95% CI, 1.52-1.64). The increased mortality associated with these complications was higher in LMICs (58.5%) than in HICs (35.4%). After controlling for coagulopathy complications, treatment intensity, and multiple other factors, the mortality was higher among patients in LMICs than among patients in HICs (odds ratio, 1.45; 95% CI, 1.39-1.51).ConclusionIn a large, international registry of patients hospitalized for COVID-19, coagulopathy complications were more frequent in HICs than in LMICs (developing countries). Increased mortality associated with coagulopathy complications was of a greater magnitude among patients in LMICs. Additional research is needed regarding timely diagnosis of and intervention for coagulation derangements associated with COVID-19, particularly for limited-resource settings.

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Pragmatic Recommendations for Therapeutics of Hospitalized COVID-19 Patients in Low- and Middle-Income Countries.

Publications

Pragmatic Recommendations for Therapeutics of Hospitalized COVID-19 Patients in Low- and Middle-Income Countries.

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