Introduction

These Treatment Guidelines have been developed to inform clinicians how to care for patients with COVID-19. Because clinical information about the optimal management of COVID-19 is evolving quickly, these Guidelines will be updated frequently as published data and other authoritative information become available.

The recommendations in these Guidelines are based on scientific evidence and expert opinion. Each recommendation includes two ratings: a letter (A, B, or C) that indicates the strength of the recommendation and a Roman numeral (I, II, or III) that indicates the quality of the evidence that supports the recommendation (see Table 1).

Panel Composition

Members of the COVID-19 Treatment Guidelines Panel (the Panel) were appointed by the Panel cochairs based on their clinical experience and expertise in patient management, translational and clinical science, and/or development of treatment guidelines. Panel members include representatives from federal agencies, health care and academic organizations, and professional societies. Federal agencies and professional societies represented on the Panel include:

American Association of Critical-Care Nurses

American College of Chest Physicians

American College of Emergency Physicians

American Society of Hematology

American Thoracic Society

Biomedical Advanced Research and Development Authority

Centers for Disease Control and Prevention

Department of Defense

Department of Veterans Affairs

Food and Drug Administration

Infectious Diseases Society of America

National Institutes of Health

Pediatric Infectious Diseases Society

Society of Critical Care Medicine

Society of Infectious Diseases Pharmacists

The inclusion of representatives from professional societies does not imply that their societies have endorsed all elements of this document.

The names, affiliations, and financial disclosures of the members and ex officio members of the Panel and members of the support team are provided in the Panel Roster and Financial Disclosure sections of the Guidelines.

Development of the Guidelines

Each section of the Guidelines is developed by a working group of Panel members with expertise in the area addressed in the section. Each working group is responsible for identifying relevant information and published scientific literature and for conducting a systematic, comprehensive review of that information and literature. The working groups propose updates to the Guidelines based on the latest published research findings and evolving clinical information.

New Guidelines sections and recommendations are reviewed and voted on by the voting members of the Panel. To be included in the Guidelines, a recommendation must be endorsed by a majority of Panel members. Updates to existing sections that do not affect the rated recommendations are approved by Panel cochairs without a Panel vote. Panel members are required to keep all Panel deliberations and unpublished data considered during the development of the Guidelines confidential.

Method of Synthesizing Data and Formulating Recommendations

The working groups critically review and synthesize the available data to develop recommendations. Aspects of the data that are considered include, but are not limited to, the source of the data, the type of study (e.g., case series, prospective or retrospective cohorts, randomized controlled trial), the quality and suitability of the methods, the number of participants, and the effect sizes observed. Each recommendation is assigned two ratings according to the scheme presented in Table 1.

Table 1. Recommendation Rating Scheme

Table 1. Recommendation Rating Scheme Strength of Recommendation Quality of Evidence for Recommendation A: Strong recommendation for the statement B: Moderate recommendation for the statement C: Optional recommendation for the statement I: One or more randomized trials with clinical outcomes and/or validated laboratory endpoints II: One or more well-designed, nonrandomized trials or observational cohort studies III: Expert opinion

It is important to note that, at present, to develop the recommendations in these Guidelines, the Panel incorporates data from the rapidly growing published scientific literature on COVID-19. The Panel also relies heavily on experience with other diseases, supplemented with evolving personal clinical experience with COVID-19.

In general, the recommendations in these Guidelines fall into the following categories:

The Panel recommends using [blank] for the treatment of COVID-19 (rating). Recommendations in this category are based on evidence from clinical trials or large cohort studies that demonstrate clinical or virologic efficacy in patients with COVID-19, with the potential benefits outweighing the potential risks.

Recommendations in this category are based on evidence from clinical trials or large cohort studies that demonstrate clinical or virologic efficacy in patients with COVID-19, with the potential benefits outweighing the potential risks. There are insufficient data for the Panel to recommend either for or against the use of [blank] for the treatment of COVID-19 (no rating). This statement is not a recommendation; it is used in cases when there are insufficient data to make a recommendation.

This statement is not a recommendation; it is used in cases when there are insufficient data to make a recommendation. The Panel recommends against the use of [blank] for the treatment of COVID-19, except in a clinical trial (rating). This recommendation is for an intervention that has not clearly demonstrated efficacy in the treatment of COVID-19 and/or has potential safety concerns. More clinical trials are needed to further define the role of the intervention.

This recommendation is for an intervention that has not clearly demonstrated efficacy in the treatment of COVID-19 and/or has potential safety concerns. More clinical trials are needed to further define the role of the intervention. The Panel recommends against the use of [blank] for the treatment of COVID-19 (rating). This recommendation is used in cases when the available data clearly show a safety concern and/or the data show no benefit for the treatment of COVID-19.

Evolving Knowledge on Treatment for COVID-19

Currently, there are no Food and Drug Administration (FDA)-approved drugs for COVID-19. However, an array of drugs approved for other indications, as well as multiple investigational agents, are being studied for the treatment of COVID-19 in clinical trials around the globe. These trials can be accessed at ClinicalTrials.gov. In addition, providers can access and prescribe investigational drugs or agents approved or licensed for other indications through various mechanisms, including Emergency Use Authorizations (EUAs), Emergency Investigational New Drug (EIND) applications, compassionate use or expanded access programs with drug manufacturers, and/or off-label use.

Whenever possible, the Panel recommends that promising, unapproved, or unlicensed treatments for COVID-19 be studied in well-designed, controlled clinical trials. This includes drugs that have been approved or licensed for other indications. The Panel recognizes the critical importance of clinical research in generating evidence to address unanswered questions regarding the safety and efficacy of potential treatments for COVID-19. However, the Panel also realizes that many patients and providers who cannot access such trials are still seeking guidance about whether to use these agents.

A large volume of data and publications from randomized controlled trials, observational cohorts, and case series are emerging at a very rapid pace, some in peer-reviewed journals, others as pre-peer-review manuscripts, and, in some cases, press releases. The Panel continuously reviews the available data and assesses their scientific rigor and validity. These sources of data and the experiences of the Panel members are used to determine whether new recommendations or changes to the current recommendations are warranted.

Finally, it is important to stress that the rated treatment recommendations in these Guidelines should not be considered mandates. The choice of what to do or not to do for an individual patient is ultimately decided by the patient with their provider.