Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug 23;8(8):CD015061.
doi: 10.1002/14651858.CD015061.

Interventions for palliative symptom control in COVID-19 patients

Marike Andreas  1 , Vanessa Piechotta  1 , Nicole Skoetz  2 , Kathrin Grummich  3 , Marie Becker  1 , Lisa Joos  4 , Gerhild Becker  4 , Winfried Meissner  5 , Christopher Boehlke  4
Affiliations

Interventions for palliative symptom control in COVID-19 patients

Marike Andreas et al. Cochrane Database Syst Rev. .

Abstract

Background: Individuals dying of coronavirus disease 2019 (COVID-19) may experience distressing symptoms such as breathlessness or delirium. Palliative symptom management can alleviate symptoms and improve the quality of life of patients. Various treatment options such as opioids or breathing techniques have been discussed for use in COVID-19 patients. However, guidance on symptom management of COVID-19 patients in palliative care has often been derived from clinical experiences and guidelines for the treatment of patients with other illnesses. An understanding of the effectiveness of pharmacological and non-pharmacological palliative interventions to manage specific symptoms of COVID-19 patients is required.

Objectives: To assess the efficacy and safety of pharmacological and non-pharmacological interventions for palliative symptom control in individuals with COVID-19.

Search methods: We searched the Cochrane COVID-19 Study Register (including Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), Embase, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), medRxiv); Web of Science Core Collection (Science Citation Index Expanded, Emerging Sources); CINAHL; WHO COVID-19 Global literature on coronavirus disease; and COAP Living Evidence on COVID-19 to identify completed and ongoing studies without language restrictions until 23 March 2021. We screened the reference lists of relevant review articles and current treatment guidelines for further literature.

Selection criteria: We followed standard Cochrane methodology as outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We included studies evaluating palliative symptom management for individuals with a confirmed diagnosis of COVID-19 receiving interventions for palliative symptom control, with no restrictions regarding comorbidities, age, gender, or ethnicity. Interventions comprised pharmacological as well as non-pharmacological treatment (e.g. acupressure, physical therapy, relaxation, or breathing techniques). We searched for the following types of studies: randomized controlled trials (RCT), quasi-RCTs, controlled clinical trials, controlled before-after studies, interrupted time series (with comparison group), prospective cohort studies, retrospective cohort studies, (nested) case-control studies, and cross-sectional studies. We searched for studies comparing pharmacological and non-pharmacological interventions for palliative symptom control with standard care. We excluded studies evaluating palliative interventions for symptoms caused by other terminal illnesses. If studies enrolled populations with or exposed to multiple diseases, we would only include these if the authors provided subgroup data for individuals with COVID-19. We excluded studies investigating interventions for symptom control in a curative setting, for example patients receiving life-prolonging therapies such as invasive ventilation. DATA COLLECTION AND ANALYSIS: We used a modified version of the Newcastle Ottawa Scale for non-randomized studies of interventions (NRSIs) to assess bias in the included studies. We included the following outcomes: symptom relief (primary outcome); quality of life; symptom burden; satisfaction of patients, caregivers, and relatives; serious adverse events; and grade 3 to 4 adverse events. We rated the certainty of evidence using the GRADE approach. As meta-analysis was not possible, we used tabulation to synthesize the studies and histograms to display the outcomes. MAIN RESULTS: Overall, we identified four uncontrolled retrospective cohort studies investigating pharmacological interventions for palliative symptom control in hospitalized patients and patients in nursing homes. None of the studies included a comparator. We rated the risk of bias high across all studies. We rated the certainty of the evidence as very low for the primary outcome symptom relief, downgrading mainly for high risk of bias due to confounding and unblinded outcome assessors. Pharmacological interventions for palliative symptom control We identified four uncontrolled retrospective cohort studies (five references) investigating pharmacological interventions for palliative symptom control. Two references used the same register to form their cohorts, and study investigators confirmed a partial overlap of participants. We therefore do not know the exact number of participants, but individual reports included 61 to 2105 participants. Participants received multimodal pharmacological interventions: opioids, neuroleptics, anticholinergics, and benzodiazepines for relieving dyspnea (breathlessness), delirium, anxiety, pain, audible upper airway secretions, respiratory secretions, nausea, cough, and unspecified symptoms. Primary outcome: symptom relief All identified studies reported this outcome. For all symptoms (dyspnea, delirium, anxiety, pain, audible upper airway secretions, respiratory secretions, nausea, cough, and unspecified symptoms), a majority of interventions were rated as completely or partially effective by outcome assessors (treating clinicians or nursing staff). Interventions used in the studies were opioids, neuroleptics, anticholinergics, and benzodiazepines. We are very uncertain about the effect of pharmacological interventions on symptom relief (very low-certainty evidence). The initial rating of the certainty of evidence was low since we only identified uncontrolled NRSIs. Our main reason for downgrading the certainty of evidence was high risk of bias due to confounding and unblinded outcome assessors. We therefore did not find evidence to confidently support or refute whether pharmacological interventions may be effective for palliative symptom relief in COVID-19 patients. Secondary outcomes We planned to include the following outcomes: quality of life; symptom burden; satisfaction of patients, caregivers, and relatives; serious adverse events; and grade 3 to 4 adverse events. We did not find any data for these outcomes, or any other information on the efficacy and safety of used interventions. Non-pharmacological interventions for palliative symptom control None of the identified studies used non-pharmacological interventions for palliative symptom control.

Authors' conclusions: We found very low certainty evidence for the efficacy of pharmacological interventions for palliative symptom relief in COVID-19 patients. We found no evidence on the safety of pharmacological interventions or efficacy and safety of non-pharmacological interventions for palliative symptom control in COVID-19 patients. The evidence presented here has no specific implications for palliative symptom control in COVID-19 patients because we cannot draw any conclusions about the effectiveness or safety based on the identified evidence. More evidence is needed to guide clinicians, nursing staff, and caregivers when treating symptoms of COVID-19 patients at the end of life. Specifically, future studies ought to investigate palliative symptom control in prospectively registered studies, using an active-controlled setting, assess patient-reported outcomes, and clearly define interventions. The publication of the results of ongoing studies will necessitate an update of this review. The conclusions of an updated review could differ from those of the present review and may allow for a better judgement regarding pharmacological and non-pharmacological interventions for palliative symptom control in COVID-19 patients.

PubMed Disclaimer

Conflict of interest statement

MA: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the CEOsys project), which was paid to the institution.

VP: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the CEOsys project), which was paid to the institution.

NS: has declared no conflict of interest.

KG: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the CEOsys project), which was paid to the institution.

MB: has declared no conflict of interest.

LJ: has declared no conflict of interest.

GB: has declared no conflict of interest. GB is a palliative care specialist.

WM: reports consultancy or talks for the following companies: Mundipharma, Grünenthal, Menarini, BioQPharma, Bionorica, Kyowa, TAD, Tilray, Sanofi, Septodont, and Northern Swan. He reports research funding from Pfizer, Mundipharma, and Grünenthal. WM is a palliative care specialist.

CB: is funded by the Federal Ministry of Education and Research, Germany (NaFoUniMedCovid19, funding number: 01KX2021; part of the CEOsys project), which was paid to the institution.

Figures

1
1
Study flow diagram.
2
2
Summary of risk of bias.
3
3
Visual synthesis of Alderman 2020
4
4
Visual synthesis for Alderman 2020
5
5
Visual synthesis for Hetherington 2020
6
6
Visual synthesis for Lovell 2020
7
7
Visual synthesis for Strang 2021a
8
8
Visual synthesis for Strang 2021a
9
9
Visual synthesis for Strang 2021a
10
10
Visual synthesis for Strang 2021b
11
11
Visual synthesis for Strang 2021b
See this image and copyright information in PMC

References

References to studies included in this review

Alderman 2020 {published and unpublished data}
    1. Alderman B, Webber K, Davies A. An audit of end-of-life symptom control in patients with corona virus disease 2019 (COVID-19) dying in a hospital in the United Kingdom. Palliative Medicine 2020;34(9):1249-55. [DOI: 10.1177/0269216320947312] - DOI - PubMed
Hetherington 2020 {published data only}
    1. Hetherington L, Johnston B, Kotronoulas G, Finlay F, Keeley P, McKeown A. COVID-19 and hospital palliative care—a service evaluation exploring the symptoms and outcomes of 186 patients and the impact of the pandemic on specialist hospital palliative care. Palliative Medicine 2020;34(9):1256-62. [DOI: 10.1177/0269216320949786] - DOI - PMC - PubMed
Lovell 2020 {published data only}
    1. Lovell N, Maddocks M, Etkind SN, Taylor K, Carey I, Vora V, et al. Characteristics, symptom management, and outcomes of 101 patients with COVID-19 referred for hospital palliative care. Journal of Pain and Symptom Management 2020;60(1):e77-81. [DOI: 10.1016/j.jpainsymman.2020.04.015] - DOI - PMC - PubMed
Strang 2021 {published data only}
    1. Strang P, Bergström J, Lundström S. Symptom relief is possible in elderly dying COVID-19 patients: a national register study. Journal of Palliative Medicine 2020;24(4):514-9. [DOI: 10.1089/jpm.2020.0249] - DOI - PubMed
    1. Strang P, Martinsson L, Bergström J, Lundström S. COVID-19: symptoms in dying residents of nursing homes and in those admitted to hospitals. Journal of Palliative Medicine 2021 Mar 5 [Epub ahead of print]. [DOI: 10.1089/jpm.2020.0688] - DOI - PubMed

References to studies excluded from this review

ACTRN12620000443998p {published data only}
    1. ACTRN12620000443998p. Home rehabilitation for people with COVID-19: implementing telehealth approaches to care. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379528&isRe... (first received 31 March 2020).
Allande Cussó 2020 {published data only}
    1. Allande Cussó R, Navarro Navarro C, Porcel Gálvez AM. Humanized care in a death for COVID-19: a case study [El cuidado humanizado en la muerte por COVID-19: a propósito de un caso]. Enfermería Clínica 2021;(31):62-7. [DOI: 10.1016/j.enfcli.2020.05.018] - DOI - PMC - PubMed
Anneser 2020 {published data only}
    1. Anneser J. Dying patients with COVID-19: what should hospital palliative care teams (HPCTs) be prepared for? Palliative & Supportive Care 2020;18(4):382-4. - PMC - PubMed
Bisson 2020 {published data only}
    1. Bisson E, Presswood E, Kenyon J, Shelton F, Hall T. Against the odds: unlikely COVID-19 recovery. BMJ Supportive and Palliative Care 3 July 2020 [Epub ahead of print]. [DOI: 10.1136/bmjspcare-2020-002477] - DOI - PubMed
Cook 2020 {published data only}
    1. Cook DJ, Takaoka A, Hoad N, Swinton M, Clarke FJ, Rudkowski JC, et al. Clinician perspectives on caring for dying patients during the pandemic: a mixed-methods study. Annals of Internal Medicine 2020 Dec 8 [Epub ahead of print]. [DOI: 10.7326/M20-6943] - DOI - PMC - PubMed
Delisle 2020 {published data only}
    1. Delisle S, Heller FE, Blinderman CD. Prolonged critical illness and demoralization: curative factors in hospice care in the age of COVID-19. Journal of Hospice & Palliative Nursing 2020;22(6):428-31. [DOI: 10.1097/NJH.0000000000000689] - DOI - PubMed
Galazzi 2020 {published data only}
    1. Galazzi A, Brioni M, Mistraletti G, Roselli P, Abbruzzese C. The last farewell by video call. Minerva Anestesiologica 2020;86(11):1254-5. [DOI: 10.23736/S0375-9393.20.14906-X] - DOI - PubMed
Haydar 2020 {published data only}
    1. Haydar A, Lo KB, Goyal A, Gul F, Peterson E, Bhargav R, et al. Palliative care utilization among patients with COVID-19 in an underserved population: a single-center retrospective study. Journal of Pain and Symptom Management 2020;60(2):e18-21. [DOI: 10.1016/j.jpainsymman.2020.05.022] - DOI - PMC - PubMed
    1. Pettus K, Lima L. Update to the fast tracked article entitled: palliative care utilization among patients with COVID-19 in an underserved population: a single-center retrospective study. Journal of Pain and Symptom Management 2020;60(4):e1. [DOI: 10.1016/j.jpainsymman.2020.07.017] - DOI - PMC - PubMed
Heath 2020 {published data only}
    1. Heath L, Yates S, Carey M, Miller M. Palliative care during COVID-19: data and visits from loved ones. Journal of Hospice and Palliative Medicine 2020;37(11):988-91. [DOI: 10.1177/1049909120943577] - DOI - PMC - PubMed
ISRCTN16561225 {unpublished data only}
    1. ISRCTN16561225. CovPall: Improving palliative care for people affected by the COVID-19 pandemic by sharing learning—the national and international response. www.isrctn.com/ISRCTN16561225 (first received 5 May 2020). [DOI: 10.1186/ISRCTN16561225] - DOI
Johnston 2020 {published data only}
    1. Johnston B, Blades S. COVID-19: using ‘knitted hearts’ in end-of-life care to enable continuing bonds and memory making. International Journal of Palliative Nursing 2020;26(8):391-3. - PubMed
Lee 2020 {published data only}
    1. Lee J, Abrukin L, Flores S, Gavin N, Romney ML, Blinderman CD, et al. Early intervention of palliative care in the emergency department during the COVID-19 pandemic. JAMA Internal Medicine 2020;180(9):1252-4. [DOI: 10.1001/jamainternmed.2020.2713] - DOI - PMC - PubMed
Lopez 2020 {published data only}
    1. Lopez S, Finuf KD, Marziliano A, Sinvani L, Burns EA. Palliative care consultation in hospitalized patients with COVID-19: a retrospective study of characteristics, outcomes, and unmet needs. Journal of Pain and Symptom Management 2021;62(2):276. [DOI: 10.1016/j.jpainsymman.2020.12.015] - DOI - PMC - PubMed
Martinsson 2021 {published data only}
    1. Martinsson L, Strang P, Bergström J, Lundström S. Were clinical routines for good end-of-life care maintained in hospitals and nursing homes during the first three months of the outbreak of COVID-19? A national register study. Journal of Pain and Symptom Management 2021;61(1):e11-9. [DOI: 10.1016/j.jpainsymman.2020.09.043] - DOI - PMC - PubMed
Mendoza 2020 {published data only}
    1. Mendoza A. Palliative care during a pandemic. www.providermagazine.com/Monthly-Issue/2020/September/Pages/Palliative-C....
Mumoli 2021 {published data only}
    1. Mumoli N, Florian C, Cei M, Evangelista I, Colombo A, Razionale G, et al. Palliative care in a COVID-19 internal medicine ward: a preliminary report. International Journal of Infectious Disease 2021;105:141-3. [DOI: 10.1016/j.ijid.2021.02.053] - DOI - PMC - PubMed
Paice 2021 {published data only}
    1. Paice JA, Wholihan D, Dahlin C, Rosa WE, Mazanec P, Long CO, et al. Palliative nursing: the core of COVID-19 care. Journal of Hospice & Palliative Nursing 2021;23(1):1-6. [DOI: 10.1097/NJH.0000000000000709] - DOI - PMC - PubMed
Pavlu 2020 {published data only}
    1. Pavlu D, DeMarco K, Sobrino-Bonilla Y. Field notes from the frontline of a COVID-19 outbreak: dyspnea management for hospitalized patients at end-of-life. Journal of Hospital & Palliative Nursing 2020;23(2):128-34. [DOI: 10.1097/NJH.0000000000000728] - DOI - PubMed
Rao 2021 {published data only}
    1. Rao A, Zaaqoq AM, Kang IG, Vaughan EM, Flores J, Avila-Quintero VJ, et al. Palliative care for patients on extracorporeal membrane oxygenation for COVID-19 infection. American Journal of Hospice and Palliative Medicine 2021 March 9 [Epub ahead of print]. [DOI: 10.1177/10499091211001009] - DOI - PMC - PubMed
Ritchey 2020 {published data only}
    1. Ritchey KC, Foy A, McArdel E, Gruenewald DA. Reinventing palliative care delivery in the era of COVID-19: how telemedicine can support end of life care. American Journal of Hospice and Palliative Medicine 2020;37(11):992-7. [DOI: 10.1177/1049909120948235] - DOI - PMC - PubMed
Riva 2020 {published data only}
    1. Riva L, Caraceni A, Vigorita F, Berti J, Martinelli MP, Crippa M, et al. COVID-19 emergency and palliative medicine: an intervention model. BMJ Supportive & Palliative Care 2020 Nov 23 [Epub ahead of print]. [DOI: 10.1136/bmjspcare-2020-002561] - DOI - PubMed
Sun 2020 {published data only}
    1. Sun H, Lee J, Meyer BJ, Myers EL, Nishikawa MS, Tischler JL, et al. Characteristics and palliative care needs of COVID‐19 patients receiving comfort‐directed care. Journal of the American Geriatrics Society 2020;68(8):1162-4. [DOI: 10.1111/jgs.16507] - DOI - PMC - PubMed
Turner 2020 {published data only}
    1. Turner J, Eliot Hodgson L, Leckie T, Eade L, Ford-Dunn S. A dual-center observational review of hospital-based palliative care in patients dying with COVID-19. Journal of Pain and Symptom Management 2020;60(2):e75-8. [DOI: 10.1016/j.jpainsymman.2020.04.031] - DOI - PMC - PubMed

References to studies awaiting assessment

ChiCTR2000029994 {unpublished data only}
    1. ChiCTR2000029994. Liu-Zi-Jue qigong and acupressure therapy for pulmonary function and quality of life in patient with severe novel coronavirus pneumonia (COVID-19): A randomized controlled trial. Chinese Clinical Trial Registry 2020. [CHICTR: 2000029994] [URL: https://www.chictr.org.cn/showprojen.aspx?proj=49309] - PMC - PubMed
    1. Zhang S, Zhu Q, Zhan C, Cheng W, Mingfang X, Fang M, et al. Acupressure therapy and Liu Zi Jue Qigong for pulmonary function and quality of life in patients with severe novel coronavirus pneumonia (COVID-19): a study protocol for a randomized controlled trial. Trials 2020;21(1):751. [DOI: 10.1186/s13063-020-04693-5] - DOI - PMC - PubMed
Groninger 2021 {unpublished data only}
    1. Groninger H, McPherson A, Vaughan E, Kang IG, Kelemen A. Hospital-based palliative care experiences of patients with COVID-19. Journal of Pain and Symptom Management 2021;61(3):695. [ABSTRACT NUMBER: SCI947] [DOI: 10.1016/j.jpainsymman.2021.01.108] - DOI
Kelly 2020 {unpublished data only}
    1. Kelly L, O’Shea N, Azhar M, Beatty S, Brennock J, Mannion E, et al. Symptomatology at the end of life with COVID-19. Abstracts of the 16th International E-Congress of the European Geriatric Medicine Society; 2020 Oct 7-9 2020 Apr 28 [Epub ahead of print]. [ABSTRACT NUMBER: 23] [DOI: 10.1007/s41999-020-00428-6] - DOI
Okuwoga 2020 {unpublished data only}
    1. Okuwoga O, Picton S, Saber S, O’Sullivan C. Managing delirium in patients with COVID-19—lessons to learn. Abstracts of the 16th International E-Congress of the European Geriatric Medicine Society; 2020 Oct 7-9 2020 Apr 28 [Epub ahead of print]. [ABSTRACT NUMBER: 281] [DOI: 10.1007/s41999-020-00428-6] - DOI

References to ongoing studies

NCT04522037 {published data only}
    1. NCT04522037. Measurement of the efficacy of morphine in the early management of dyspnea in COVID-19 positive patients (CODYS). clinicaltrials.gov/ct2/show/NCT04522037 (first received 21 August 2020).

Additional references

Antunes 2014
    1. Antunes B, Harding R, Higginson IJ. Implementing patient-reported outcome measures in palliative care clinical practice: a systematic review of facilitators and barriers. Palliative Medicine 2014;28(2):158-75. [DOI: 10.1177/0269216313491619] - DOI - PubMed
Balshem 2011
    1. Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. Journal of Clinical Epidemiology 2011;64(4):401-6. [DOI: 10.1016/j.jclinepi.2010.07.015] - DOI - PubMed
Banzett 2000
    1. Banzett RB, Mulnier HE, Murphy K, Rosen SD, Wise RJ, Adams L. Breathlessness in humans activates insular cortex. Neuroreport 2000;11(10):2117-20. [DOI: 10.1097/00001756-200007140-00012] - DOI - PubMed
Barnes 2016
    1. Barnes H, McDonald J, Smallwood N, Manser R. Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness. Cochrane Database of Systematic Reviews 2016, Issue 3. Art. No: CD011008. [DOI: 10.1002/14651858.CD011008] - DOI - PMC - PubMed
Barron 2012
    1. Barron EA, Holmes J. Delirium within the emergency care setting, occurrence and detection: a systematic review. Emergency Medicine Journal 2013;30(4):263-8. [DOI: 10.1136/emermed-2011-200586] - DOI - PubMed
Bausewein 2020
    1. Bausewein C, Voltz R, Steffen S, Radbruch L. Evidence-based guideline: Palliative care for patients with incurable cancer. www.leitlinienprogramm-onkologie.de/fileadmin/user_upload/Downloads/Leit... (accessed 26 July 2021). [AWMF-REGISTRATION NUMBER: 128/001OL]
Buchanan 2009
    1. Buchanan GF, Richerson GB. Role of chemoreceptors in mediating dyspnea. Respiratory Physiology and Neurobiology 2008;176(1):9-19. [DOI: 10.1016/j.resp.2008.12.002] - DOI - PMC - PubMed
Buitrago‐Garcia 2020
    1. Buitrago-Garcia D, Egli-Gany D, Counotte MJ, Hossmann S, Imeri H, Ipekci Aziz M, et al. Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: a living systematic review and meta-analysis. PLOS Medicine 2020;17(9):e1003346. [DOI: 10.1371/journal.pmed.1003346] - DOI - PMC - PubMed
Campbell 2020
    1. Campbell M, McKenzie JE, Sowden A, Katikireddi SV, Brennan SE, Ellis S, et al. Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ 2020;368(l6890):1-6. [DOI: 10.1136/bmj.l6890] - DOI - PMC - PubMed
Challen 2021
    1. Challen R, Brooks-Pollock E, Read JM, Dyson L, Tsaneva-Atanasova K, Danon L. Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study. BMJ 2021;327(n579):1-10. [DOI: 10.1136/bmj.n579] - DOI - PMC - PubMed
COMET 2020
    1. Core outcome set developers’ response to COVID-19 (2nd April 2020). www.comet-initiative.org/Studies/Details/1538 (accessed 9 April 2020).
Crombeen 2020
    1. Crombeen AM, Lilly EJ. Management of dyspnea in palliative care. Current Oncology 2020;27(3):142-5. [DOI: 10.3747/co.27.6413.] - DOI - PMC - PubMed
Deeks 2021
    1. Deeks JJ, Higgins JP, Altman DG. Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook.
EPOC 2017
    1. Cochrane Effective Practice and Organisation of Care (EPOC). What study designs can be considered for inclusion in an EPOC review and what should they be called? EPOC Resources for review authors. Available from epoc.cochrane.org/resources/epoc-resources-review-authors (accessed 23 April 2019).
Forni 2021
    1. Forni G, Mantovani A. COVID-19 vaccines: where we stand and challenges ahead. Cell Death & Differentiation 2021;28:626-39. [DOI: 10.1038/s41418-020-00720-9] - DOI - PMC - PubMed
Gaertner 2017
    1. Gaertner J, Siemens W, Meerpohl JJ, Antes G, Meffert C, Xander C, et al. Effect of specialist palliative care services on quality of life in adults with advanced incurable illness in hospital, hospice, or community settings: systematic review and meta-analysis. BMJ 2017;375:1-14. [DOI: 10.1136/bmj.j2925] - DOI - PMC - PubMed
Griffin 2013
    1. Griffin CE 3rd, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner Journal 2013;13(2):214-23. [PMID: ] - PMC - PubMed
Haun 2017
    1. Haun MW, Estel S, Rücker G, Friederich HC, Villalobos M, Thomas M, et al. Early palliative care for adults with advanced cancer. Cochrane Database of Systematic Reviews 2017, Issue 6. Art. No: CD011129. [DOI: 10.1002/14651858.CD011129.pub2] - DOI - PMC - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60. [DOI: 10.1136/bmj.327.7414.557] - DOI - PMC - PubMed
Higgins 2021
    1. Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook. - PMC - PubMed
Huang 2020
    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497-506. [DOI: 10.1016/S0140-6736(20)30183-5] - DOI - PMC - PubMed
Hui 2020
    1. Hui D, De La Rosa A, Wilson A, Nguyen T, Wu J, Delgado-Guay M, et al. Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit: a single-centre, double-blind, parallel-group, randomised trial. Lancet Oncology 2020;21(7):989-98. [DOI: 10.1016/S1470-2045(20)30307-7] - DOI - PMC - PubMed
Johns Hopkins 2021
    1. Johns Hopkins University of Medicine Coronavirus Resource Center. Mortality analyses. coronavirus.jhu.edu/data/mortality (accessed 16 April 2021).
Johnson 2020
    1. Johnson MJ, Currow DC. Opioids for breathlessness: a narrative review. BMJ Supportive & Palliative Care 2020;10:287-95. [DOI: 10.1136/bmjspcare-2020-002314] - DOI - PubMed
Keeley 2020
    1. Keeley P, Buchanan D, Carolan C, Pivodic L, Tavabie S, Noble S. Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary. BMJ Supportive & Palliative Care 2020;10(4):381-4. [DOI: 10.1136/bmjspcare-2020-002368] - DOI - PubMed
Kennedy 2020
    1. Kennedy M, Helfand BKI, Gou RY, Gartaganis SL, Webb M, Moccia JM, et al. Delirium in older patients with COVID-19 presenting to the emergency department. JAMA Network Open 2020;3(11):e2029540. [DOI: 10.1001/jamanetworkopen] - DOI - PMC - PubMed
Kreuzberger 2020
    1. Kreuzberger N, Hirsch C, Chai KL, Piechotta V, Valk SJ, Estcourt LJ, et al. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database of Systematic Reviews 2021, Issue 1. Art. No: CD013825. [DOI: 10.1002/14651858.CD013825] - DOI - PMC - PubMed
Lefebvre 2021
    1. Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M-I, et al. Chapter 4: Searching for and selecting studies. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook.
Li 2021
    1. Li T, Higgins JPT, Deeks JJ. Chapter 5: Collecting data. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook.
Liang 2020
    1. Liang W, Guan W, Chen R, Wang W, Li J, Xu K, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet 2020;21(3):335-7. [DOI: 10.1016/S1470-2045(20)30096-6] - DOI - PMC - PubMed
MAGICapp 2020 [Computer program]
    1. MAGIC Evidence Ecosystem Foundation MAGICapp: A digital authoring and publication platform for the evidence ecosystem. MAGIC Evidence Ecosystem Foundation, 2020. Available at app.magicapp.org/.
Mahler 2013
    1. Mahler DA, Gifford AH, Waterman LA, Ward J, Kraemer WJ, Kupchak BR, et al. Effect of increased blood levels of β-endorphin on perception of breathlessness. Chest 2013;143(5):1378-85. [DOI: 10.1378/chest.12-1541] - DOI - PubMed
McKenzie 2021
    1. McKenzie JE, Brennan SE. Chapter 12: Synthesizing and presenting findings using other methods. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook.
Meagher 2018
    1. Meagher D, Agar MR, Teodorczuk A. Debate article: Antipsychotic medications are clinically useful for the treatment of delirium. International Journal of Geriatric Psychiatry 2018;33:1420-7. [DOI: 10.1002/gps.4759] - DOI - PubMed
Mercadamte 2014
    1. Mercadamte S. Death rattle: critical review and research agenda. Support Care Cancer 2014;22(2):571-5. [DOI: 10.1007/s00520-013-2047-5] - DOI - PubMed
Microsoft 2018 [Computer program]
    1. Excel. Microsoft Corporation. Microsoft Corporation, 2018. Available at office.microsoft.com/excel.
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Journal of Clinical Epidemiology 2009;62(10):1006-12. - PubMed
Mottiar 2020
    1. Mottiar M, Hendin A, Fischer L, des Ordons AR, Hartwick M. End-of-life care in patients with a highly transmissible respiratory virus: implications for COVID-19. Canadian Journal of Anaesthesia 2020;67:1-7. [DOI: 10.1007/s12630-020-01699-0] - DOI - PMC - PubMed
Mulder 2019
    1. Mulder RL, Bresters D, Van den Hof M, Koot BG, Castellino SM, Loke YK, et al. Hepatic late adverse effects after antineoplastic treatment for childhood cancer. Cochrane Database of Systematic Reviews 2019, Issue 4. Art. No: CD008205. [DOI: 10.1002/14651858.CD008205.pub3] - DOI - PMC - PubMed
Nehls 2020
    1. Nehls W, Delis S, Haberland B, Maier BO, Sänger K, Tessmer G, et al. Management of patients with COVID-19—recommendations from a palliative care perspective. Pneumologie 2020;774(10):652-9. [DOI: 10.1055/a-1156-2759] - DOI - PMC - PubMed
NICE 2020
    1. National Institute for Health and Care Excellence (NICE). Managing COVID-19 symptoms (including at the end of life) in the community: summary of NICE guidelines. BMJ 2020;369:m1461. [DOI: 10.1136/bmj.m1461] - DOI - PubMed
Ouzzani 2016
    1. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Systematic Reviews 2016;5(1):210. [DOI: 10.1186/s13643-016-0384-4] - DOI - PMC - PubMed
Parmar 1998
    1. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Statistics in Medicine 1998;17(24):2815-34. [DOI: 10.1002/(SICI)1097-0258(19981230)] - DOI - PubMed
Pattinson 2009
    1. Pattinson KT, Governo RJ, MacIntosh BJ, Russell EC, Corfield DR, Tracey I, et al. Opioids depress cortical centers responsible for the volitional control of respiration. Journal of Neuroscience 2009;29(25):8177-86. [DOI: 10.1523/JNEUROSCI.1375-09.2009] - DOI - PMC - PubMed
Radbruch 2020
    1. Radbruch L, De Lima L, Knaul F, Wenk R, Ali Z, Bhatnaghar S, et al. Redefining palliative care—a new consensus-based definition. Journal of Pain and Symptom Management 2020;60(4):754-64. [DOI: 10.1016/j.jpainsymman.2020.04.027] - DOI - PMC - PubMed
Reeves 2021
    1. Reeves BC, Deeks JJ, Higgins JPT, Shea B, Tugwell P, Wells GA. Chapter 24: Including non‐randomized studies on intervention effects. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook.
RevMan Web 2021 [Computer program]
    1. The Cochrane Collaboration Review Manager Web (RevMan Web). Version 3.6.0. The Cochrane Collaboration, 2021. Available at revman.cochrane.org.
Santesso 2020
    1. Santesso N, Glenton C, Dahm P, Garner P, Akl EA, Alper B, et al. GRADE guidelines 26: Informative statements to communicate the findings of systematic reviews of interventions. Journal of Clinical Epidemiology 2020;1(119):126-35. [DOI: 10.1016/j.jclinepi.2019.10.014] - DOI - PubMed
Schünemann 2019
    1. Schünemann HJ, Cuello C, Akl EA, Mustafa RA, Meerpohl JJ, Thayer K, et al. GRADE guidelines: 18. How ROBINS-I and other tools to assess risk of bias in nonrandomized studies should be used to rate the certainty of a body of evidence. Journal of Clinical Epidemiology 2019;111:105-14. [DOI: 10.1016/j.jclinepi.2018.01.012] - DOI - PMC - PubMed
Schünemann 2021
    1. Schünemann HJ, Higgins JPT, Vist GE, Glasziou P, Akl EA, Skoetz N, et al. Chapter 14: Completing ‘Summary of findings’ tables and grading the certainty of the evidence. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook.
Shelby‐James 2012
    1. Shelby-James TM, Hardy J, Agar M, Yates P, Mitchell G, Sanderson C, et al. Designing and conducting randomized controlled trials in palliative care: a summary of discussions from the 2010 clinical research forum of the Australian Palliative Care Clinical Studies Collaborative. Palliative Medicine 2012;26(8):1042-7. [DOI: 10.1177/0269216311417036] - DOI - PubMed
Siemieniuk 2020
    1. Siemieniuk R, Rochwerg B, Agoritsas T, Lamontagne F, Leo YS, Macdonald H, et al. A living WHO guideline on drugs for covid-19. BMJ 2020;370:m3379. [DOI: 10.1136/bmj.m3379] - DOI - PubMed
Sterne 2016
    1. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016;355:1-7. [DOI: 10.1136/bmj.i4919] - DOI - PMC - PubMed
Sterne 2019
    1. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366(l4898):1-8. [DOI: 10.1136/bmj.l4898] - DOI - PubMed
Struyf 2020
    1. Struyf T, Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Leeflang MM, et al. Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease. Cochrane Database of Systematic Reviews 2020, Issue 7. Art. No: CD013665. [DOI: 10.1002/14651858.CD013665] - DOI - PMC - PubMed
Svenska Palliativregistret 2021
    1. The Swedish Register of Palliative Care (SRPC). www.palliativ.se (accessed prior to 9 August 2021).
Taskforce NCCE 2021
    1. Taskforce NCCE. Clinical Care Guidance. covid19evidence.net.au/ (accessed prior to 9 August 2021).
Tierney 2007
    1. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 2007;8:16. [DOI: 10.1186/1745-6215-8-16] - DOI - PMC - PubMed
Ting 2020
    1. Ting R, Edmonds P, Higginson IJ, Sleeman KE. Palliative care for patients with severe covid-19. BMJ 2020;370:m2710. [DOI: 10.1136/bmj.m2710] - DOI - PubMed
Valk 2020a
    1. Valk SJ, Piechotta V, Chai KL, Doree C, Monsef I, Wood EM, et al. Convalescent plasma or hyperimmune immunoglobulin for people with COVID‐19: a living systematic review. Cochrane Database of Systematic Reviews 2021, Issue 5. Art. No: CD013600. [DOI: 10.1002/14651858.CD013600.pub4] - DOI - PMC - PubMed
Valk 2020b
    1. Valk SJ, Piechotta V, Kimber C, Chai KL, Monsef I, Doree C, et al. Convalescent plasma and hyperimmune immunoglobulin to prevent infection with SARS-CoV-2. Cochrane Database of Systematic Reviews 2021, Issue 1. Art. No: CD013802. [DOI: 10.1002/14651858.CD013802] - DOI
von Leupoldt 2007
    1. Leupoldt A, Dahme B. Psychological aspects in the perception of dyspnea in obstructive pulmonary diseases. Respiratory Medicine 2007;101(3):411-22. [DOI: 10.1016/j.rmed.2006.06.011] - DOI - PubMed
WHO 2007
    1. World Health Organization (WHO). Cumulative number of reported probable cases of SARS. www.who.int/csr/sars/country/2003_07_11/en/ (accessed 13 April 2020).
WHO 2019
    1. World Health Organization (WHO). Middle East respiratory syndrome coronavirus (MERS-CoV). www.who.int/emergencies/mers-cov/en/ (accessed 13 April 2020).
WHO 2020a
    1. World Health Organization (WHO). Report of the WHO‐China Joint Mission on coronavirus disease 2019 (COVID‐19). www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-... (accessed prior to 9 August 2021).
WHO 2020b
    1. World Health Organization (WHO). Estimating mortality from COVID-19—scientific brief. www.who.int/publications/i/item/WHO-2019-nCoV-Sci-Brief-Mortality-2020.1 (accessed 2 November 2020).
WHO 2020c
    1. World Health Organization (WHO). Palliative care. www.who.int/news-room/fact-sheets/detail/palliative-care (accessed 13 July 2021).
WHO 2021a
    1. World Health Organization (WHO). WHO Coronavirus Disease (COVID-19) Dashboard. covid19.who.int (accessed 14 July 2021).
WHO 2021b
    1. World Health Organization (WHO). Weekly epidemiological update—13 July. www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-1... (accessed 14 July 2021).
WHO 2021c
    1. World Health Organization (WHO). COVID-19 Clinical management: living guidance. www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 (accessed 15 April 2021).
WHO 2021d
    1. World Health Organization (WHO). Draft landscape of COVID-19 candidate vaccines. www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-va... (accessed 15 April 2021).
WHO 2021e
    1. World Health Organization (WHO). Therapeutics and COVID-19: living guideline. Version 6.1. app.magicapp.org/#/guideline/nBkO1E (accessed 15 July 2021).
Williamson 2020
    1. Williamson E, Walker AJ, Bhaskaran KJ, Bacon S, Bates C, Morton CE, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 2020;584:430-6. [DOI: 10.1038/s41586-020-2521-4] - DOI - PMC - PubMed
Wouters 2021
    1. Wouters OJ, Shadlen KC, Salcher-Konrad M, Pollard AJ, Larson HJ, Teerawattananon Y, et al. Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment. Lancet 2021;10278:1023-34. [DOI: 10.1016/S0140-6736(21)00306-8] - DOI - PMC - PubMed
Wu 2020
    1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323(13):1239-42. [DOI: 10.1001/jama.2020.2648] - DOI - PubMed

References to other published versions of this review

Andreas 2021
    1. Andreas M, Piechotta V, Becker G, Metzendorf M-I, Skoetz N, Meissner W, et al. Palliative symptom management in Covid-19 patients: a systematic review. PROSPERO. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021233630. 2021. - PMC - PubMed

Publication types