COVID-19 Published Guidelines and Reviews
The COVID-19 Scientific Advisory Board has compiled and examined published guidelines and reviews on COVID-19 and have provided a collection of those most helpful and relevant for frontline providers below. New guidelines and reviews will be added to this page on a recurring basis.
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- A Game Plan for the Resumption of Sport and Exercise After Coronavirus Disease 2019 (COVID-19) Infection. 5/13/20. Phelan. JAMA Cardiology.
Expert consensus opinion from members of the American College of Cardiology’s Sports & Exercise Cardiology Council, with input from national leaders in sports cardiology, regarding when those recovered from COVID-19 can return to recreational or competitive sports. Acute cardiac injury, based on elevated troponin, EKG changes, or ECHO abnormalities, occur in up to 22% of hospitalized COVID-19 patients. After myocarditis, return to play should require “normalization of ventricular function, absence of biomarker evidence of inflammation, and absence of inducible arrhythmias.” ECHO, stress testing, and rhythm monitoring are used to determine risk stratification after 3-6 months of exercise restriction. An algorithm is provided based on COVID-19 testing and symptoms: 1) Asymptomatic COVID-19 positive athletes or those who have detected antibodies indicating prior infection can slowly resume activity after 2 weeks; 2) If mild or moderate symptoms, a minimum of 2 weeks cessation of exercise training after symptoms resolve is recommended, and if cardiovascular evaluation including cardiac biomarkers and imaging reveal evidence of cardiac involvement, myocarditis return-to-play guidelines should be followed; 3) For those who were hospitalized or had more severe COVID-19, myocarditis return-to-play guidelines should be followed, and if cardiac biomarkers and imaging are normal after cardiac reevaluation graded, resumption of exercise can start at a minimum of 2 weeks after symptom resolution.
- AGA Institute Rapid Review of the GI and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19. 5/1/20. Sultan. Gastroenterology.
This is an excellent paper from the American Gastroenterological Association for frontline workers wanting to understand and care for patients with GI disease during the COVID-19 pandemic. It starts with a detailed meta-analysis (47 studies with 10,890 patients) of GI symptoms and abnormal LFTs in patients with COVID-19. Overall, 10% of COVID-19 patients had GI symptoms and 15% had elevations of AST and/or ALT. Both GI symptoms and elevated LFTs were more common outside China. Occasionally, GI symptoms presented before other COVID-19 symptoms. Though fecal RT-PCR testing is commonly positive, culture of SARS-CoV-2 is rarely successful. Numerous tables are included, such as the GI side effects of commonly used COVID-19 drugs. Based on all pooled information, guidelines are presented for frontline providers dealing with GI symptoms in the COVID-19 era. These include, among others, checking for other etiologies of GI symptoms in outpatients, following LFTs on COVID-19 inpatients, not testing stool, and following outpatients with GI symptoms alone in case they develop COVID-19.
- Anesthesia ICU Transition Materials. University of Utah.
Four videos lasting over three hours, from the University of Utah, designed to update the ICU knowledge of anesthesiologists (and others) in preparation for a COVID-19 surge. These are well done, thorough and very clinically applicable. Discussions cover most topics from PPE to self-care and sustainable staffing, to specifics of ventilator management and more.
- ASA’s Statements and Recommendations on COVID-19. American Society of Anesthesiologists.
- Cases of Cerebral Venous Sinus Thrombosis with Thrombocytopenia after Receipt of the Johnson & Johnson COVID-19 Vaccine. Centers for Disease Control and Prevention.
- Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study. 9/29/20. Webb BJ. Lancet Rheumatol.
Defining the scourge of COVID-19 hyperinflammatory syndrome. 9/29/20. Cron RQ. Lancet Rheumatol.
These authors are first to propose specific criteria for COVID-19-associated hyperinflammatory (cytokine storm) syndrome (cHIS). They validated the cHIS scale using retrospective data from 299 COVID-19 inpatients from their 22-hospital system. The six-criterion additive scale: fever, macrophage activation (hyperferritinemia), hematological dysfunction (neutrophil to lymphocyte ≥10:1 ratio), hepatic injury (lactate dehydrogenase or aspartate aminotransferase), coagulopathy (D-dimer), and cytokinemia (C-reactive protein, interleukin-6, or triglycerides). Meeting ≥2 criteria was associated with increased mortality and mechanical ventilation risk. External validation is needed. The cHIS scale may better target populations for trials and immunomodulation and diminish heterogeneity of treatment effect analyses of trials with undifferentiated patients.
- Coronavirus Disease 2019 (COVID-19) Resource List. US Food & Drug Administration.
- COVID-19 Associated Thrombosis and Coagulopathy: Review of the Pathophysiology and Implications for Antithrombotic Management. 11/24/20. Ortega-Paz L. J Am Heart Assoc.
This is a comprehensive, well-written, albeit lengthy, review of COVID-19 pathophysiology and therapies. Cardiovascular, thrombotic, and coagulopathic manifestations are emphasized along with the importance of individual risk assessment for venous thromboembolism (VTE). Multiple validated VTE risk assessment tools are enumerated. A theory of imbalanced ACE/ACEII receptors as a risk factor for SARS-CoV-2 infection is discussed. Useful summary figures and tables include knowledge gaps and ongoing areas of research.
- COVID-19 Evidence Hub. Center for Science in the Public Interest.
Includes an International database of studies, study results and assessment of study results on COVID-19.
- COVID-19 Information for Health Care Professionals. American Society of Anesthesiologists.
- COVID-19-Related Guidance Documents for Industry, FDA Staff, and Other Stakeholders. US Food & Drug Administration.
- COVID-19 Webcast Series. Society of Critical Care Medicine.
- Determination of brain death/death by neurologic criteria: the World Brain Death Project. 8/30/20. Sung GY. JAMA.
Published by a panel of 40+ international experts, this is a thorough and comprehensive guideline aiming to establish worldwide recognized brain death criteria and testing methods.
- Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19. May 12. Liang. JAMA Intern Med.
Developed a prediction model for composite end point of ICU admit, need for a ventilator, and death based on ten variables: cxray abnormality, age, hemoptysis, dyspnea, unconsciousness, # of comorbidities, cancer hx, neutrophil/lymphocyte ratio, LDH, and direct bilirubin.
- Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study. 1/11/21. Gupta R. Lancet Resp Med.
ISARIC4C is a global initiative with the purpose of preventing illness and death from infectious disease outbreaks. This article presents information on development and validation of a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalized adults with suspected or confirmed COVID-19 prospectively recruited to ISARIC4C study across 260 hospitals in England, Scotland, and Wales. The authors contend that the 4C Deterioration model, designed to be used on admission, has strong potential for clinical utility and generalizability to predict clinical deterioration and inform decision-making among adults hospitalized with COVID-19. The Mortality and Deterioration calculator can be accessed with the following link: isaric4c.net/risk/.
SAB Comment: While the SAB does not endorse management strategies or interventions, its members believe this manuscript and accompanying calculator to evaluate risk of disease progression or death MAY be useful in supplementing case management decisions.
- Development of Severe COVID-19 Adaptive Risk Predictor (SCARP), a Calculator to Predict Severe Disease or Death in Hospitalized Patients With COVID-19. 3/1/21. Wongvibulsin S. Ann Intern Med.
This article presents a simple web-based calculator for the risk of developing severe disease (requiring high-flow nasal oxygen, non-invasive or mechanical ventilation) or of death in the following day or in the following week. The input values include only the worst O2 saturation, and highest O2 flow rate in the last 6 hours and in the last 24 hours, plus, for milder cases, the absolute neutrophil and lymphocyte count. Development was facilitated by a machine learning tool used to analyze 105 parameters from 3294 patients hospitalized from May to December in Baltimore area hospitals. The final calculator requiring only the above few measures showed an area under the curve (AUC) of 0.89 for one-day predictions and 0.83-0.87 for one-week predictions.
- Difficult Airway Management in Adult COVID-19 Patients: Statement by the Society of Airway Management. 3/12/2021. Foley LJ. Anesth Analg.
This statement represents recommendations by the Society for Airway Management task force for the difficult airway management of adults with COVID-19 with the goal to optimize successful airway management while minimizing the risk of clinician exposure. Extensive discussion of almost all aspects of difficult intubations is summarized by three pages of tables, which outline, among other things, an emphasis on preparedness, proper PPE, awake intubation, extubation, equipment and drugs.
- Guiding Principles for the Conduct of Observational Critical Care Research for Coronavirus Disease 2019 Pandemics and Beyond: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study Registry. 9/15/20. Walkey AJ. Crit Care Med.
The article describes developed guiding principles for use of observational data. Topics covered include research workforce and infrastructure, rapid, harmonized data collection, processes for choosing research questions, state-of-the-art observational methods, accounting for random error, innovative peer-review pathways, and implementation/improvement. It is likely to be a valuable, timely tool during the current pandemic and beyond.
- Improving clinical management of COVID-19: the role of prediction models. 1/11/21. Wynants L. Lancet Resp Med.
This is an editorial indicating that the main clinical advantage of the ISARIC4C predictive model is that required patient specific data is available from daily routine care and may help inform stratification of patients on the basis of clinical severity. In combination, the 4C Deterioration and Mortality models could be utilized in creating an evidence-based clinical pathway for patients with COVID-19. Validated predictive models may improve clinical management and resource utilization.
- Individualizing Risk Prediction for Positive COVID-19 Testing: Results from 11,672 Patients. 6/20/20. Jehi L. Chest.
The authors of this article developed an online risk calculator that can identify individualized risk of a positive COVID-19 test. All patients from Cleveland Clinic in Ohio and Florida were tested, not just those who had the disease. Findings included: lower risk for Asians vs whites; lower risk for those who had pneumococcal polysaccharide vaccine and flu vaccine; higher risk with poor socioeconomic status; and reduced risk of testing positive in patients who were on melatonin, carvedilol, and paroxetine.
- Long COVID
Robert N. Sladen, MBChB, FCCM on behalf of the IARS Scientific Advisory BoardOne of the most challenging yet enigmatic aspects of the COVID-19 pandemic is the increasing recognition of prolonged impairment of functional capacity for weeks or months after the initial illness. Like many a “new” entity, it is categorized by a plethora of descriptors, including Long COVID, Long-haul COVID, post-acute COVID-19 Syndrome (PACS) or post-acute sequelae of SARS-CoV-2 infection (PASC). Others simply describe “persistent poor health” or “long-term symptoms.”
Early in the pandemic information on “long-haulers” was spread via social media in the lay community who often met with skepticism from their primary care providers1. Self-reporting by respected physicians has changed attitudes,2, 3 together with published case reports and multiple retrospective studies. Reports from Italy and China revealed symptoms in nearly 90% of discharged hospitalized patients at 60 days4 and 75% at six months,5 but it is now recognized that these symptoms may occur in up to 30% of nonhospitalized patients.6-8 No association has been found between persistent respiratory symptoms in COVID-19 survivors and initial disease severity.9
Reported symptoms run the entire gamut of pathophysiology, the most prominent being chronic fatigue (similar to myalgic encephalomyelitis ME/CFS10), “brain fog,” insomnia, depression, altered mood, dyspnea on exertion, cardiac arrhythmias, anosmia, tinnitus and alopecia among others.11 Physician-sufferers have drawn attention to a myriad chronic or relapsing conditions, including myocarditis, thromboembolic disease, new onset diabetes, thyroiditis and allergies, and autonomic dysfunction such as postural orthostatic tachycardia syndrome (POTS).12
In the US, there is increasing recognition of the impact of Long COVID on healthcare and many clinics have opened to provide support for patients. In May 2020, Mount Sinai Medical Center opened its Center for Post-COVID Care,13 and others have followed. In the United Kingdom, the National Health Service has posted a list of common symptoms14 and provides considerable supportive information on “Your COVID Recovery” on its website. Recently, the Centers for Disease Control (CDC) held a webinar on Clinician Experience with Post-Acute COVID-19 Care.15
Many questions regarding the etiology of Long COVID remain. One of the most perplexing aspects is that many patients with Long COVID have had very mild or even asymptomatic infection.6, 7 Why do some patients develop it and others do not? A large study based on a mobile app suggests that early multisystem symptoms, older age and female sex are predictors of Long COVID.16 Could some long-term symptoms simply represent the lingering physical effects of severe illness and multiorgan injury17 and their psychological consequences such as postintensive care syndrome or PTSD?18, 19 How might these differ from long-term effects after SARS or MERS20 or other historic influenza epidemics?21 Could they be due to persistence of a host viral reservoir even if SARS-CoV-2 testing is negative, or viral fragments that stimulate a persistent aberrant auto-immune response?
A host of published studies have examined aspects of Long COVID, including respiratory, neurologic, auditory and other manifestations. Some even tie in previously unclear syndromes such as POTS.22 Most recently, an extraordinarily comprehensive multidisciplinary review was published in Nature Medicine.11 It provides extensive discussion on available evidence and knowledge for every organ system, a list of relevant studies and publications and also a series of simple, clear graphics that provide an easily understandable overview of the problem. On a practical level, there is increasing awareness that COVID-19 survivors may need ongoing medical and community support, especially in the light of stigma, discrimination, depression and PTSD, akin to cancer survivors.23, 24 Support groups and digital communities for sufferers of Long COVID are forming on social media.25 The UK National Institute for Health and Care Excellence (NICE) has established guidelines for managing the long-term effects of COVID-19.26 The World Health Organization (WHO) has called upon countries to offer more rehabilitation and has developed a clinical platform case report form for “post COVID-19 condition.”27
A number of large-scale research endeavors are being developed to explore Long COVID. The NIH recently announced a $1.15 billion initiative to study PASC.28 In the UK, the Post-Hospitalization COVID Study (PHOSP-COVID) is being led by a national consortium to gather long-term prospective data on 10,000 patients after hospital discharge.29 A 42-country multinational open access study linked to the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) is being developed to specifically focus on the long-term consequences of COVID-19.30
In sum, there is still much to be learned about the long-lasting effects of COVID-19. What has become abundantly clear is that the personal and public health impact of Long COVID will linger long after the acute pandemic has subsided.
- Editorial. Long COVID: let patients help define long-lasting COVID symptoms. Nature. 2020;586:170. https://www.nature.com/articles/d41586-020-02796-2.
- Garner P. Paul Garner: For 7 weeks I have been through a roller coaster of ill health, extreme emotions, and utter exhaustion. thebmjopinion. 2020. https://blogs.bmj.com/bmj/2020/05/05/paul-garner-people-who-have-a-more-protracted-illness-need-help-to-understand-and-cope-with-the-constantly-shifting-bizarre-symptoms/.
- Garner P. Paul Garner: on his recovery from long covid. thebmjopinion. 2021. https://blogs.bmj.com/bmj/2021/01/25/paul-garner-on-his-recovery-from-long-covid/.
- Carfi A, Bernabei R, Landi F. Gemelli Against COVID-19 Post Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020;324:603. https://jamanetwork.com/journals/jama/fullarticle/2768351.
- Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397:220-32. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32656-8/fulltext.
- Graham EL, Clark JR, Orban ZS, et al. Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized Covid-19 “long haulers”. Ann Clin Transl Neurol. 2021. https://onlinelibrary.wiley.com/doi/full/10.1002/acn3.51350.
- Jacobson KB, Rao M, Bonilla H, et al. Patients with uncomplicated COVID-19 have long-term persistent symptoms and functional impairment similar to patients with severe COVID-19: a cautionary tale during a global pandemic. Clin Infect Dis. 2021. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab103/6129932/.
- Logue JK, Franko NM, McCulloch DJ, et al. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open. 2021;4:e210830. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776560.
- Townsend L, Dowds J, O’Brien K, et al. Persistent poor health Post-COVID-19 is not associated with respiratory complications or initial disease severity. Ann Am Thorac Soc. 2021. https://www.atsjournals.org/doi/10.1513/AnnalsATS.202009-1175OC.
- Nath A. Long-Haul COVID. Neurology. 2020;95:559-60. https://n.neurology.org/content/95/13/559.
- Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021. https://www.nature.com/articles/s41591-021-01283-z.
- Gorna R, MacDermott N, Rayner C, et al. Long COVID guidelines need to reflect lived experience. Lancet. 2021;397:455-7. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32705-7/fulltext.
- Center for Post-COVID Care at Mount Sinai. COVID-19 Facts and Resources. 2020. Accessed April 12, 2021. https://www.mountsinai.org/about/covid19/center-post-covid-care.
- NHS. Long-term effects of coronavirus (long COVID). 2021. Accessed April 12, 2021. https://www.nhs.uk/conditions/coronavirus-covid-19/long-term-effects-of-coronavirus-long-covid/.
- Kahn I, COCA, CDC. COCA Call: Treating Long COVID: Clinician Experience with Post-Acute COVID-19 Care. 2021. Accessed April 12, 2021. https://emergency.cdc.gov/coca/ppt/2021/012821_transcript.pdf.
- Sudre CH, Murray B, Varsavsky T, et al. Attributes and predictors of long COVID. Nat Med. 2021. https://www.nature.com/articles/s41591-021-01292-y.
- Marshall M. The lasting misery of coronavirus long-haulers. Nature. 2020;585:339-41. https://www.nature.com/articles/d41586-020-02598-6.
- Sykes DL, Holdsworth L, Jawad N, Gunasekera P, Morice AH, Crooks MG. Post-COVID-19 Symptom Burden: What is Long-COVID and How Should We Manage It? Lung. 2021. https://link.springer.com/article/10.1007/s00408-021-00423-z.
- Naidu SB, Shah AJ, Saigal A, et al. The high mental health burden of “Long COVID” and its association with on-going physical and respiratory symptoms in all adults discharged from hospital. Eur Respir J. 2021. https://erj.ersjournals.com/content/early/2021/02/11/13993003.04364-2020.
- Vittori A, Lerman J, Cascella M, et al. COVID-19 Pandemic Acute Respiratory Distress Syndrome Survivors: Pain After the Storm? Anesth Analg. 2020;131:117-9. https://journals.lww.com/anesthesia-analgesia/pages/articleviewer.aspx?year=2020&issue=07000&article=00019&type=Fulltext.
- Stefano GB. Historical insight into infections and disorders associated with neurological and psychiatric sequelae similar to Long COVID. Med Sci Monit. 2021;27:e931447. https://www.medscimonit.com/abstract/full/idArt/931447.
- Johansson M, Stahlberg M, Runold M, et al. Long-Haul Post-COVID-19 Symptoms Presenting as a Variant of Postural Orthostatic Tachycardia Syndrome: The Swedish Experience. JACC Case Rep. 2021. https://www.sciencedirect.com/science/article/pii/S2666084921001005?via%3Dihub.
- Ernst M, Brahler E, Beutel ME. How can we support COVID-19 survivors? Five lessons from long-term cancer survival. Public Health. 2021. https://www.sciencedirect.com/science/article/pii/S0033350621000123?via%3Dihub.
- Iqbal FM, Lam K, Sounderajah V, Elkin S, Ashrafian H, Darzi A. Understanding the survivorship burden of long COVID. EClinicalMedicine. 2021;33:100767. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00047-X/fulltext.
- Yan W. Understanding the Long-Term Impacts of COVID-19 in Survivors. IEEE Pulse. 2021;12:19-23. https://ieeexplore.ieee.org/document/9359551.
- Sivan M, Taylor S. NICE guideline on long covid. BMJ. 2020;371:m4938. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00031-X/fulltext.
- Wise J. Long covid: WHO calls on countries to offer patients more rehabilitation. BMJ. 2021;372:n405. https://www.bmj.com/content/372/bmj.n405.
- Subbaraman N. US health agency will invest $1 billion to investigate ‘long COVID’. Nature. 2021;591:356. https://www.nature.com/articles/d41586-021-00586-y.
- The Post-hospitalisation COVID-19 study (PHOSP-COVID). Accessed April 12, 2021. https://www.phosp.org.
- Sigfrid L, Cevik M, Jesudason E, et al. What is the recovery rate and risk of long-term consequences following a diagnosis of COVID-19? A harmonised, global longitudinal observational study protocol. BMJ Open. 2021;11:e043887. https://bmjopen.bmj.com/content/11/3/e043887.
- NIH COVID-19 Treatment Guidelines
- NIH Launches Platform to Serve as Depository for COVID-19 Medical Data. 7/29/20. Rubin R. JAMA.
Though not a research article, the news report, based on an NIH news release, summarizes an NIH effort to store and study medical record data from people across the country who have been diagnosed with coronavirus disease 2019. Certainly, research articles will be published in the future that will be based on this effort. For more information for institutions on how to contribute data, visit https://ncats.nih.gov/n3c/about/program-faq.
- Open Critical Care COVID-19 Resources Hub
This is a comprehensive, well-organized, web-based compendium of COVID-19 care and epidemic response guidelines along with learning modules. It summarizes and provides links to COVID-19-care recommendations from the WHO, CDC, NIH, IDSA, SCCM, NEJM, UpToDate, and Partners In Health, among others. The site is led by the UCSF Center for Health Equity in Surgery & Anesthesia with support of the United States Agency for International Development (USAID) and STAR Program, and aims to provide healthcare workers with coordinated, high-quality information and learning tools regarding the care of critically ill COVID-19 patients that are open-access and continuously updated. Each section is also available in Spanish, and some material is available in multiple additional languages.
Sections include the following, along with many more resources:
- COVIDprotocols.org: Adaptable (though not fully peer-reviewed) protocols for the management of COVID-19 patients was created through a collaboration of Brigham & Women’s Hospital, UCSF’s Institute for Global Health Services, Partners in Health, and Open Critical Care. Content is relevant to all practice settings. Topics include testing, infection prevention and control, PPE, patient assessment, outpatient, inpatient and critical care management, obstetrics, pediatrics, and post-COVID care, among others. Features include frequent updates and an “Ask an Expert” chat service. The Spanish language version is here.
- COVID-19 Guidelines Dashboard: This reference tool provides practitioners a quick, intuitively navigable look at current care and pharmacotherapy guidelines from leading healthcare authorities. Stop-light color coding indicates the level of concordance among authorities for each therapy. Date lines and hyperlinked references are included. It promises to be expandable and updated frequently. The Spanish language version is available here.
- Respiratory Care Pocket Card: This link downloads the latest version of a printable, concise summary of oxygen and ventilator therapies, a collaboration of multiple institutions including the UCSF Anesthesia Division of Global Health Equity and USAID. The easy-to-use table format reviews commonly required respiratory care management including non-invasive forms of oxygen delivery, how to calculate ideal body weight, key ventilator modes and settings, how to assess and treat ventilator/patient dyssynchrony, and much more. Relevant references and links are embedded, many (including the card itself) via QR codes that may be useful after printing. The Spanish language version is available here.
- Oxygen Supply and Demand Calculator: This valuable tool for clinicians and administrators balances individual patient use with facility requirements to help maintain a safe O2 supply. It provides an estimate of total facility hourly oxygen consumption and calculates reserves after the user provides the number of hypoxic patients, modes of treatment, and a few details about the oxygen supply infrastructure. Imputed individual patient PO2, PF ratio, and the nonlinear SpO2:FiO2 ratio can be estimated by selecting a patient’s FiO2 and O2 saturation. The Spanish language version is available here.
- Prediction models for covid-19 outcomes. 10/21/2020. Sperrin M. BMJ.
A risk prediction algorithm to estimate hospital admission (n=10,776) and mortality (n=4,384) from covid-19 was created and validated using a UK dataset derived from 6.08 million 19-100 year old patients and validated with data from an additional 2.17 million. Study period was Jan 24-April 30 for the initial cohort and May 1-June 30, 2020 for the validation cohort. The model, including age, ethnicity, deprivation, BMI, and a range of comorbidities, predicted ¾ of deaths with excellent discrimination (Harrell’s C statistics >0.9). People in the top 20% of predicted risk of death accounted for 94% of deaths.
- Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. 10/21/2020. Clift AK. BMJ.
Editorial discussing the potential utility of prediction models referencing article 1528 and a second BMJ report published in September on the 4C mortality score (calculated at hospital admission to predict in-hospital mortality for patients with confirmed or likely covid-19). Models have serious shortcomings and require constant updating however may also inform public health policies, vaccine allocation, and provide decision support for treatment.
- Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. 10/21/2020. Clift AK. BMJ.
- Predictors of failure with high-flow nasal oxygen therapy in COVID-19 patients with acute respiratory failure: a multicenter observational study. 3/6/21. Mellado-Artigas R. J Intensive Care.
The authors developed a simple online tool to predict the eventual need for intubation and mechanical ventilation in patients treated with high-flow nasal oxygen (HFNO) based on the outcome of 259 patients from 36 Spanish and Andorran intensive care units. Inputs required include those from the SOFA score (platelet count, bilirubin, mean arterial pressure, Glasgow Comma Scale, creatinine, and FiO2) plus SpO2 and respiratory rate. Performance measured by area under the curve was 0.88, (95% CI 0.80-0.96).
- Provisional Mortality Data – United States, 2020. 4/8/2021. Ahmad FB. MMWR Morb Mortal Wkly Rep.
The estimated age-adjusted death rate in the US increased by 15.9% from 2019 to 2020, representing the first increase since 2017. COVID-19 caused or contributed to 377,883 or 11.3% of total death and ranked third behind heart disease (21%) and cancer (17%). When sorted by age, race, ethnicity and sex, this report by the CDC’s National Vital Statistics System found age-adjusted death rates to be highest in the over 85-year old population, the non-Hispanic Black and the non-Hispanic American Indian or Alaska Native people. Males died at 33% higher rate from COVID than females.
These provisional data are the result of a streamlined reporting mechanism which provides expanded mortality data for 2020 with a mere 4 month (prior 11 month) delay.
- Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score. 9/10/20. Knight SR. BMJ.
Observational study utilizing the Coronavirus Clinical Characterization Consortium Mortality Score (Model-4C) to assess mortality in two groups of COVID-19 patients, using health data from 260 UK hospitals. Both groups demonstrated 32.2% mortality (February to May, N= 35,463 and May to June, N=22,361). The Model-4C Mortality Score incorporates 8 clinical admission criteria: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein. The score showed high discrimination for mortality with an ROC of 0.79. Relevant statistics, graphs and tables are included in the article.
- SARS-CoV-2-Associated Deaths Among Persons Aged <21 Years – United States, February 12-July 31, 2020. 9/18/20. Bixler D. MMWR Morb Mortal Wkly Rep.
This CDC Morbidity and Mortality Weekly Report describing deaths in <21 year old population. Most patients are Hispanic or Black, and 45% had 2 or more associated illnesses. Most of the deaths occurred in 18-20 year olds. Of curiosity, only 8% exhibited the inflammatory illness possibly due to the large number that died out-of-hospital or in the ER. Most significant is that although 391,814 cases were reported in the age group, only 121 deaths occurred, a fatality rate of 0.08%.
- Should Remdesivir Be Used for the Treatment of Patients With COVID-19? Rapid, Living Practice Points From the American College of Physicians (Version 2). 2/9/21. Qaseem A. Ann Intern Med.
This clinical guideline updates the 10/5/2020 version, based on a U.S. Dept. of Veterans Affairs Evidence Synthesis Program review through 12/7/2020. Target patients include all hospitalized, non-pregnant, adults with COVID-19. Current evidence suggests an overall modest net benefit of remdesivir for patients who require oxygen but not invasive mechanical ventilation (IMV) or ECMO at initiation, and suggests that 5-day treatment may be as effective as 10 days, without increased harm. Recovery is modestly better and more rapid and serious adverse events are modestly reduced. Mortality is slightly reduced. Evidence quality was low-moderate in all RCTs.
- Begin 5 days of remdesivir for hospitalized patients requiring oxygen but not IMV or ECMO.
- Extend remdesivir to 10 days if IMV or ECMO is initiated during the 5-day course.
SAB Comment: A NEJM study published 12/11/20, titled, Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19, and highlighted in our newsletter issue 47, indicates that dual therapy with remdesivir and the anti-inflammatory baricitinib was found to be superior to remdesivir alone.
- Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update. 2/8/21. Alhazzani W. Crit Care Med.
This is an update of the published Society of Critical Care Medicine (SCCM) Surviving Sepsis Guidelines for COVID-19 therapy and management. A multinational task force (43 experts; 14 countries) reviewed guidelines; three new and six revised are included. Rationale was included in discussions. This is a good reference and resource for latest SCCM guidelines, incorporating the best available evidence.
- Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)
Robert N. Sladen, MBChB, FCCM on behalf of the IARS Scientific Advisory Board
In recent weeks a great deal of attention has been directed to cases, some of them fatal, of major venous thrombosis associated with thrombocytopenia occurring within 1-3 weeks after initial immunization with the AstraZeneca modified adenovirus vaccine for COVID-19. Although extremely rare relative to the large numbers vaccinated, cases have been more prominent in younger (less than 50 years old), previously healthy patients in Germany and the United Kingdom. In the United States, six similar cases have been reported after immunization with the Johnson & Johnson modified adenovirus vaccine, which has been put on pause pending investigation by the FDA.
In an observational study published in the New England Journal of Medicine (NEJM) on April 16, Dr. Marie Scully and her colleagues report finding pathologic antibodies to platelet factor 4 (PF4) in 22 of 23 patients who suffered thromboembolism and thrombocytopenia after receiving the AstraZeneca vaccine1. Patients also had highly elevated levels of D-dimer with low or normal fibrinogen. The unexpected finding of anti-PF4 antibodies is identical to that of heparin-induced thrombocytopenia (HIT), but in the absence of administered heparin, and is referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). The mechanism of induction of anti-PF4 antibodies is as yet unknown. As with HIT, use of heparin to treat the thromboses or platelet transfusion for thrombocytopenia worsens thrombosis. Instead, the authors recommend avoidance of platelet transfusions together with a combination of nonheparin anticoagulation and intravenous immunoglobulin and consideration for high-dose glucocorticoids. If there is evidence of thrombosis and thrombocytopenia with elevated D-dimer (>4000 FEU), low or normal fibrinogen and no evidence of an alternate diagnosis, they advocate early treatment as above pending results of anti-PF4 antibody testing by HIT ELISA testing or functional HIT assay.
In an accompanying editorial2, Drs. Cines and Bussel review this and two other reports previously published in the NEJM3,4, a total of 39 patients with cerebral venous sinus, portal, splanchnic or hepatic vein thrombosis who had a 40% mortality. At the current time, a total of 223 possible cases of cerebral venous sinus or splanchnic vein thrombosis have been reported among 34 million recipients of the AstraZeneca vaccine, but not all of these cases have been subjected to rigorous review or tested for anti-PF4 antibodies. The authors point out that we do not yet know how the vaccine elicits the production of anti-PF4 antibodies, nor whether these antibodies are directly responsible for platelet activation and thrombus formation. Anti-PF4 antibodies are detected in 25-50% of patients after cardiovascular surgery, but the incidence of HIT is very uncommon and even then is rarely associated with cerebral venous sinus or abdominal venous thrombosis. The low prevalence of this serious complication must be weighed against the benefits of preventing COVID-19 in the larger population.
On April 16, the American Society of Hematology (ASH) published new guidelines, which will be regularly updated, on the diagnosis and recommended therapy of VITT5. Their recommendation is that urgent evaluation for VITT should be commenced on patients with severe, recurrent or persistent symptoms of headache, abdominal pain, nausea and vomiting, vision changes, shortness of breath, and/or leg pain and swelling that have an onset 4-20 days after vaccination. While VITT has not been reported following the mRNA Pfizer or Moderna vaccines, the ASH recommends immediate evaluation for VITT in any patient presenting with this constellation of symptoms following any COVID-19 vaccination. If initial evaluation reveals thrombocytopenia or thrombosis, an urgent hematology consultation is recommended with avoidance of heparin until VITT has been ruled out.References
- Scully M, Singh D, Lown R, Poles A, Solomon T, Levi M, et al. Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination. N Engl J Med. April 2021. https://www.nejm.org/doi/10.1056/NEJMoa2105385.
- Cines DB, Bussel JB. SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia. N Engl J Med. April 2021. https://www.nejm.org/doi/10.1056/NEJMe2106315.
- Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N Engl J Med. April 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2104840.
- Schultz NH, Sorvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F, Ahlen MT, et al. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. N Engl J Med. April 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2104882.
- Bussell J, Connors JM, DCines DB, Dunbar CE, Michaelis LC, Kreuziger LB, Lee AYY, Pabinger I. Vaccine-induced Immune Thrombotic Thrombocytopenia: Frequently Asked Questions. American Society of Hematology. Updated April 19, 2021. Accessed April 21, 2021. https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia.
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