Expert guidance on the management and challenges of long-COVID syndrome: a systematic review

ABSTRACT

Introduction

Long-COVID is a condition characterized by the permanence of symptoms beyond 4 weeks after an initial infection. It affects 1 out of 5 people and is loosely related to the severity of acute infection and pathological mechanisms, which are yet to be understood.

Areas covered

This article looks at currently available and under-studied therapies for long-COVID syndrome. It particularly gives focus to ongoing trials and reviews the underlying mechanisms. A comprehensive literature search was performed on PubMed and clincaltrial.gov of clinical trials concerning the management of long-COVID syndrome.

Expert opinion

‘Long-COVID’ syndrome is a new emergency characterized by several symptoms such as fatigue, dyspnea, cognitive and attention disorders, sleep disorders, post-traumatic stress disorder, muscle pain, and concentration problems. Despite the many guidelines available to date, there are no established treatments of long-COVID. Pharmacological research is studying known drugs that act on the reduction or modulation of systemic inflammation, or innovative drugs used in similar pathologies. Rehabilitation now seems to be the safest treatment to offer, whereas we will have to wait for the pharmacological research trials in progress as well as plan new trials based on a better understanding of the pathogenic mechanisms.

KEYWORDS:

• Long COVID syndrome
• post COVID
• COVID-19
• Post-Acute COVID-19 syndrome

Acronymous

6MWT, the 6-minute walk test; ATA, Atmosphere Absolute; CBD, Cannabidiol; CCR5 C-C, Chemokine Receptor Type 5; CDC, Centers for Disease Control and Prevention; COPD, Chronic Obstructive Pulmonary Disease; CoQ10, Coenzyme Q10; COVID-19, Coronavirus disease 2019; DLco, Lung Diffusion of Carbon Oxide; DNA, Deoxyribonucleic Acid; FEV_1, Forced Expiratory Volume in the 1 second; FVC, Forced Vital Capacity; HBOT, Hyperbaric Oxygen Therapy; HIV, Human Immunodeficiency Virus; IFN, Interferon; IL, Interleukin; LDN, Low Dose Naltrexone; NAD+, Nicotinamide Adenine Dinucleotide; NICE, National Institute for Health and Care Excellence; PACS, Post Acute COVID-19 Syndrome; PCS, Post COVID-19 Syndrome; PRISMA-P, Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol; SAE, Severe Adverse Events; SaO_2, Arterial Saturation of Oxygen; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; THC, Tetrahydrocannabinol; TNF-α, Tumor Necrosis Factor-Alpha; UK, United Kingdom; US, United States; WHO, World Health Organization

Acknowledgments

We would like to thank Mrs. Maryann Huckvale for checking the English in the manuscript.

Article Box

• There are several definitions of Long-COVID based on the time and persistence of symptoms beyond the acute phase of infection

• No certified therapies for long-COVID have been approved, there are only expert opinion recommendations

• There are several ongoing clinical trials that are based on hypothetical mechanisms or similarities with previous diseases, but none of them have been published

• Rehabilitation seems to be the most efficient non-pharmacological cure that can be proposed

• The lack of knowledge of the pathogenetic mechanism of long-COVID seems to be the main reason for a clear line of research

Declaration of Interest

J Ora has participated as a speaker in scientific meetings and courses under the sponsorship of AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, and Novartis. P Rogliani has participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma, and Novartis. Her department was funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon. E Puxeddu has participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, and Novartis. L Calzetta has participated as advisor in scientific meetings under the sponsorship of Boehringer Ingelheim and Novartis, received non-financial support by AstraZeneca, received a research grant partially funded by Boehringer Ingelheim, Novartis and Almirall, and is or has been a consultant to Edmond Pharma, Zambon and Verona Pharma. His department was funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by institutional fundings (University of Rome ‘Tor Vergata,’ Rome, Italy).