COVID 19: Interim Guidance on Management Pending Empirical - American Thoracic Society
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COVID‐19: Interim Guidance on Management Pending Empirical
Evidence. From an American Thoracic Society‐led International
Task Force
*
Kevin C. Wilson1,2, Sanjay H. Chotirmall3, Chunxue Bai4, and Jordi Rello5
on behalf of the International Task Force on COVID‐19
1
Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA; 2 American
Thoracic Society, New York, New York, USA; 3 Lee Kong Chian School of Medicine, Nanyang Technological
University, Singapore; 4 Zhongshan Hospital, Fudan University, Shanghai Respiratory Research Institute,
Shanghai, China; 5 Clinical Research/Epidemiology in Pneumonia and Sepsis (CRIPS), Vall d'Hebron Institut of
Research (VHIR), Barcelona, Spain.
Disclosures: KCW is co‐developer of the Convergence of Opinion on Recommendations and Evidence (CORE)
process that is utilized in the guidance document and serves at the Chief of Guidelines and Documents for the
American Thoracic Society. SHC, CB, and JR have nothing to disclose.
*
Correspondence:
Kevin C. Wilson, MD
Chief of Guidelines and Documents, American Thoracic Society
Professor of Medicine, Boston University School of Medicine
Email: kwilson@thoracic.org, kcwilson@bu.edu
Note to readers: There is little empirical evidence to guide management of COVID‐19. However, with 80,000
new cases being confirmed daily and the rate still increasing, clinicians taking care of patients with COVID‐19
need guidance now. We convened an international task force of clinicians from academic centers on the
frontline of COVID‐19 management to make consensus suggestions on controversial topics. The suggestions
are based upon scarce direct evidence, indirect evidence, and clinical observations. The goal is to improve
outcomes and facilitate research by standardizing care. The suggestions provided in this document do not
constitute official positions of the American Thoracic Society or the institutions of the participants, and they
should never be considered mandates as no suggestion can incorporate all potential clinical circumstances.
The suggestions are interim guidance and will be reevaluated as evidence accumulates.
Abstract
Background: Coronavirus Disease 2019 (COVID‐19) is Methods: An International Task Force was
an acute respiratory disease caused by the composed, consisting of clinicians from academic
coronavirus, SARS‐CoV‐2. There is a paucity of centers active in COVID‐19 patient care. Consensus
empirical evidence to guide the management of suggestions were derived using the electronic
COVID‐19, but clinical observations are accumulating. decision‐making portion of the Convergence of
Consensus recommendations can help standardize Opinion on Recommendations and Evidence (CORE)
care and improve outcomes. process.
1 Updated April 3, 2020Results: The task force recommended collecting data treatment with remdesivir, lopinavir‐ritonavir,
and comparing outcomes among COVID‐19 patients tocilizumab, or systemic corticosteroids.
who received an intervention to those who did not Conclusions: The task force made suggestions based
receive the intervention using appropriate methods upon scarce direct evidence, indirect evidence, and
for causal inference and control of confounders. clinical experience. Each suggestion will be
Suggestions were made to treat hospitalized patients reconsidered as relevant evidence, particularly
who have COVID‐19 and severe pneumonia with randomized trials, are published.
hydroxychloroquine or chloroquine on a case‐by‐case Citation: Wilson KC, Chotirmall SH, Bai C, Rello J.
basis if certain requirements are present, and to COVID‐19: Interim Guidance on Management
utilize prone ventilation and extracorporeal Pending Empirical Evidence. Last updated April 3,
membrane oxygenation (ECMO) in patients with 2020. Available at
refractory hypoxemia due to COVID‐19 pneumonia www.thoracic.org/professionals/clinical‐
(i.e., acute respiratory distress syndrome [ARDS]). resources/disease‐related‐resources/covid‐19‐
The task force made no suggestions for or against guidance.pdf.
Introduction upon systematic reviews of the individuals and 80 agreed to
evidence. Such consensus guidance participate (84% acceptance rate).
Coronavirus Disease 2019 may standardize care and improve The lone reason for declining was
(COVID‐19) is an acute respiratory outcomes. The suggestions provided being too busy with patient care
disease caused by the coronavirus, in this document do not constitute responsibilities.
SARS‐CoV‐2. There is little direct official positions of the American Consensus suggestions were
evidence to inform management of Thoracic Society or the institutions of derived using the electronic decision‐
COVID‐19. The International Task the participants. They should not be making portion of the Convergence of
Force strongly agrees with prevailing considered mandates, as no Opinion on Recommendations and
sentiment that clinical trials are suggestion can incorporate all Evidence (CORE) process. The CORE
urgently needed to effectively guide potential clinical circumstances. All process is a consensus‐based
management. However, most suggestions will be revisited as approach to making clinical
patients do not have access to clinical evidence accumulates. recommendations that has been
trials, trials take time, and speculation shown to yield recommendations that
is that results will not be available Methods are concordant with
until late spring or early fall. As a recommendations developed using
result, institutions and clinicians on An International Task Force Institute of Medicine‐adherent
the frontline are utilizing a variety of was composed from March 19‐22, methodology; it has been described in
approaches to manage COVID‐19 2020. Invitations were initially sent to detail elsewhere.1,2 Briefly,
patients outside of a clinical trial, members of the American Thoracic SurveyMonkey® software
ranging from supportive care alone to Society (ATS) who are clinically active (SurveyMonkey, San Mateo, CA) was
prescribing unproven medications. in medical centers that are involved in used to create a multiple‐choice
Pending the results of clinical COVID‐19 patient care. Those invitees survey. Each survey question
trials, this document is aimed at were asked to suggest additional consisted of three parts: 1)
providing interim guidance for participants on the frontlines, with an presentation of the question in a
therapeutic interventions to frontline emphasis on pulmonologists, medical modified PICO (Patient, Intervention,
clinicians, based upon scarce direct intensivists, and infectious disease Comparator, Outcomes) format, 2) a
evidence, indirect evidence, and the experts from areas most stricken by multiple‐choice question asking for a
observations and experiences of COVID‐19. Clinicians were asked to strong or weak recommendation for
clinicians around the world who have abstain from questions outside their or against a course of action, or no
battled COVID‐19; they are not based expertise. Invitations were sent to 95
2 Updated April 3, 2020recommendation, and 3) a free‐text Suggestions compared those who did not receive
box for comments. the intervention. This can be done at
The survey was initially 1. The International Task Force the institutional, local, national, or
administered from March 23‐25, suggests that data be collected from international level. Such data will
2020. A second survey was then COVID‐19 patients who receive one provide interim guidance until
constructed that was identical to the or more of the interventions superseded by randomized trial
first, except results from the first suggested in this document, in a results when available.
round were added: a) the proportion manner that enables studies that use
of participants who selected each valid methods for causal inference For patients with COVID‐19 who are
multiple‐choice option, b) and control of confounders. The data well‐enough to be managed as
representative comments from the should be assessed periodically so outpatients, we make no suggestion
participants, and c) references that patients who received the either for or against
provided by the participants. The intervention can be compared those hydroxychloroquine (or
survey was re‐administered from who did not receive the intervention. chloroquine). 18% for intervention,
March 26‐30, 2020. Seventy‐three of Management should be modified as‐ 36% no suggestion, and 46% against
the 80 task force members completed needed based upon the intervention.
the surveys (91% response rate). comparisons.
Agreement on directionality was For hospitalized patients with
tabulated for each multiple‐choice Rationale. There is an immediate COVID‐19 who have no evidence of
question. For example, if 5, 20, 50, 13, need to determine which pneumonia, we make no suggestion
and 12 individuals selected a strong interventions against COVID‐19 are either for or against
recommendation for, weak effective and safe. Ideally, this would hydroxychloroquine (or
recommendation for, no be done through randomized trials chloroquine). 8% for intervention,
recommendation, weak and there are many such trials in 50% no suggestion, and 42% against
recommendation against, and strong progress. In the meantime, unproven intervention.
recommendation against, therapies are being administered off‐
respectively, the results were label or on a compassionate use basis. For hospitalized patients with
reported as 25% for the intervention, When data are not collected in such COVID‐19 who have evidence of
50% neither for nor against the situations, it is a missed opportunity. pneumonia, we suggest
intervention, and 25% against the The International Task Force hydroxychloroquine (or chloroquine)
intervention. At least 70% agreement recommends that data be collected on a case‐by‐case basis.
on directionality was necessary to from COVID‐19 patients who receive Requirements include all of the
make a consensus suggestion. This one or more of the interventions following: a) shared decision‐making
threshold optimizes the concordance suggested in this document. Ideally, in which the patient is informed
of CORE‐derived consensus data collection will include detailed about the possible benefits and
recommendations with Institute of information about interventions, potential side effects, b) collection of
Medicine‐adherent guideline outcomes, and patient characteristics data in a manner that enables
recommendations1. to enable analysis using appropriate studies that use valid methods for
Following the tabulation of results, methods of causal inference and to causal inference and control of
the manuscript was written. The control for confounding. Important confounders for the purpose of
suggestion was based upon the outcomes include mortality, ICU interim assessment, c) the patient’s
tabulated results, the rationale was length of stay, hospital length of stay, clinical condition is sufficiently
extrapolated from participants’ intubation rate, length of mechanical severe to warrant investigational
comments, and the description of ventilation, need for long‐term therapy, and d) there is not a
what other organizations are saying oxygen therapy, and adverse events. shortage of drug supply. 73% for
was based upon a survey of other The data should be assessed intervention, 16% no suggestion, and
organizations’ websites. periodically so that patients who 11% against intervention.
received the intervention can be
3 Updated April 3, 2020Evidence of pneumonia is defined these medications that are needed prescribing hydroxychloroquine or
as radiographic opacities or, if a chest for other legitimate purposes. Other chloroquine in hospitalized COVID‐19
radiograph has not been performed, members extrapolated from the patients with severe pneumonia. This
an SpO2 of 94% or less accompanied Grading of Recommendations, was adequate agreement to make a
by symptoms and signs of infection. Assessment, Development, and consensus suggestion for
Rationale for question. Evaluation (GRADE) framework for hydroxychloroquine or chloroquine in
Hydroxychloroquine and chloroquine making recommendations in the hospitalized patients with COVID‐19
have been shown to have in vitro context of low or very‐low quality pneumonia given the a priori decision
activity against SARS‐CoV‐2, with evidence and concluded that that 70% agreement would yield a
hydroxychloroquine being more treatment is reasonable because suggestion; had we chosen a
potent3,4. Clinical trials, however, severe COVID‐19 pneumonia is a threshold of 75% or 80%, the result
provide an inconsistent message. potentially lethal disease, would have been no suggestion.
Small controlled clinical trials from hydroxychloroquine or chloroquine The trade‐off between waiting for
more than ten hospitals in China might be beneficial, and the chance of evidence before deciding whether to
reportedly indicate that chloroquine harm is low9. The latter group administer a therapy and utilizing a
is superior to controls in preventing emphasized that the adverse effects therapy while awaiting evidence isn’t
pneumonia, improving lung imaging profile of hydroxychloroquine and unique; however, it is magnified by
findings, hastening conversion to a chloroquine are well established the urgency of a pandemic10. The
virus‐negative state, and shortening including QT interval prolongation tension is probably best solved by
the duration of disease5. However, (less likely with hydroxychloroquine creating evidence during routine
two of the trials are now publicly than chloroquine), hepatic and renal patient care, while awaiting clinical
available and they have important abnormalities, and trial results. The task force, therefore,
limitations: in a negative trial, both immunosuppression. QT interval concluded that data should be
arms included patients who had prolongation is more likely among collected in a manner that enables
undergone treatment with anti‐viral patients who receive multiple studies that use valid methods for
drugs6 and, in a positive trial, the medications with propensity to causal inference and control of
arms of the trial had important increase the QT interval, including confounders, so that interim
baseline differences7. A small azithromycin which many clinicians assessment may occur, and
controlled trial from France reported are using in combination with management adjusted accordingly.
that hydroxychloroquine hastens hydroxychloroquine or chloroquine. Comments by the task force during
conversion to a virus‐negative state, Patients can be monitored for the survey and manuscript
but important limitations included a adverse effects with routine tests; preparation provided essential
lack of patients with severe illness, however, such testing increases conditions for the suggestion. The
lack of blinding, no randomization, patient‐clinician interaction and task force urged shared decision‐
and loss to follow‐up8. laboratory personnel exposure, making in which the patient is
Results. The task force was roughly increasing the risk of transmission. informed about the possible benefits
divided into two perspectives. Some The results are notable for a shift and potential side effects. There were
members concluded that neither toward treatment with concerns that “hospitalized patients
hydroxychloroquine nor chloroquine hydroxychloroquine or chloroquine as with COVID‐19 and pneumonia” was
should be administered without the severity of COVID‐19 increased, too broad of a population;
proven benefit in COVID‐19; rather, indicating that the perceived balance subsequent consensus was that the
clinicians should wait until the results of potential benefits to harms patient’s illness should be severe
of randomized trials are known, changed as severity of illness enough to warrant investigational
otherwise there is a possibility that an increased. Fewer than 20% of the therapy. Several individuals who did
ineffective and potentially harmful task force suggested using the not vote to suggest
medication may be inappropriately medications in outpatients or hydroxychloroquine or chloroquine in
administered on a large scale, hospitalized patients without COVID‐19 patients with pneumonia
potentially leading to shortages of pneumonia, but nearly 75% suggested indicated that they would have voted
4 Updated April 3, 2020to use the medications if the illness either for or against treatment with SOLIDARITY trial includes a remdesivir
was even more severe, such as the remdesivir. 68% for intervention, 26% arm. The CDC has not taken a position
patient being severely hypoxemic or no suggestion, and 5% against on remdesivir but describes options
requiring high levels of conventional intervention. for obtaining it for hospitalized
oxygen, high‐flow oxygen, non‐ patients with COVID‐19 and
invasive mechanical ventilation, or Rationale for question. Remdesivir pneumonia. The FDA reports that it
invasive mechanical ventilation. The has in vitro activity against SARS‐CoV‐ has been working with the maker of
task force emphasized that patients 23 and related viruses including remdesivir to find multiple pathways
should be monitored closely for MERS‐CoV12,13, SARS‐CoV13, and other to study the drug under the FDA’s
adverse effects and a low threshold coronaviruses13. investigational new drug
maintained for discontinuing the Results. The differing perspectives requirements and to provide the drug
medications if adverse effects arise. described above for to patients under emergency use. The
Finally, the task force stated that the hydroxychloroquine and chloroquine Surviving Sepsis Campaign made no
suggestion should be revised as‐ also existed with remdesivir. recommendation for or against
necessary as new evidence arises. Supporting the perspective that remdesivir due to insufficient
What others are saying. The World favored waiting for randomized trial evidence11.
Health Organization (WHO) has data before deciding whether to
warned against the use medications prescribe remdesivir in COVID‐19 3. For hospitalized patients with
that have not been proven in an RCT; pneumonia were concerns about the COVID‐19 who have evidence of
its SOLIDARITY trial includes a unknown adverse effect profile of pneumonia, we make no suggestion
chloroquine arm. The United States remdesivir (in contrast to either for or against treatment with
Centers for Disease Control and hydroxychloroquine and chloroquine lopinavir‐ritonavir. 30% for
Prevention (CDC) says, “There are no for which there are decades of clinical intervention, 26% no suggestion, and
currently available data from RCTs to experience) and the uncertainty 43% against intervention.
inform clinical guidance on the use, regarding timing of initiation and
dosing, or duration of duration of therapy. Rationale for question. Lopinavir
hydroxychloroquine for prophylaxis It is noteworthy that 68% of the has both in vitro and in vivo activity
or treatment of SARS‐CoV‐2 task force favored treatment against MERS‐CoV14,15, while the
infection.” The United States Food remdesivir, if available, which was lopinavir‐ritonavir combination has in
and Drug Administration (FDA) stated one vote shy of enough agreement to vitro activity against SARS‐CoV16,17. In
that there is insufficient evidence to make a consensus suggestion. Several humans with SARS, lopinavir‐ritonavir
support treatment of COVID‐19 with task force members indicated that reduces viral load and the risk of
hydroxychloroquine or chloroquine, radiographic evidence of pneumonia acute respiratory distress syndrome
but issued an emergency‐use alone was insufficient to warrant a (ARDS) or death18. In a randomized
authorization to allow both donated suggestion to initiate remdesivir; trial of 199 patients with COVID‐19,
drugs "to be distributed and however, they would have voted to patients who received lopinavir‐
prescribed by doctors to patients with use the medication in conditions ritonavir improved more quickly, had
COVID‐19, as appropriate, when a severe enough to warrant a shorter length of ICU stay, and had
clinical trial is not available or investigational therapy, such as lower mortality than patients who
feasible." The Surviving Sepsis patients who are severely hypoxemic received standard care; however,
Campaign made no recommendation or requiring high levels of while the differences would have
for or against hydroxychloroquine or conventional oxygen, high‐flow been clinically important if real, the
chloroquine due to insufficient oxygen, non‐invasive mechanical trial was too small to definitively
evidence11. ventilation, or invasive mechanical confirm or exclude an effect (i.e., the
ventilation. findings were not statistically
2. For hospitalized patients with What others are saying. The WHO significant)19.
COVID‐19 who have evidence of has not taken a position on the use of Results. A plurality of the task
pneumonia we make no suggestion remdesivir in COVID‐19 but its force was against the administration
5 Updated April 3, 2020of lopinavir‐ritonavir to hospitalized Health Commission for use in COVID‐ suggestion against systemic
patients with COVID‐19 and 19 patients with elevated IL‐6 levels. corticosteroids. The task force
pneumonia, reflecting the lack of Results. Most task force members emphasized that the question was
definitive benefit and evidence of elected to make no suggestion, about systemic corticosteroids for the
frequent gastrointestinal side effects concluding that evidence of beneficial specific treatment of COVID‐19 in
in the RCT. However, the amount of effects in other IL‐6 mediated general. The task force did not
agreement was insufficient to reach diseases is insufficient to warrant use address systemic steroids
consensus on a formal suggestion in COVID‐19 at this time. The task administered at different points
against lopinavir‐ritonavir, reflecting force agreed, however, that clinical during the disease course or systemic
the opinion of some task force trials are worthwhile. steroids administered for the
members that, if the RCT had been What others are saying. The WHO, treatment of comorbid conditions,
larger, some of the favorable point CDC, and FDA have not taken a such as COPD exacerbations or ARDS;
estimates may have reached position on the use of tocilizumab in some clinical practice guidelines
statistical significance. COVID‐19, although the FDA recommend systemic corticosteroids
What others are saying. The WHO approved an RCT comparing for moderate to severe early
has not taken a position on the use of tocilizumab to standard care. The ARDS11,27.
lopinavir‐ritonavir in COVID‐19 but its Surviving Sepsis Campaign made no What others are saying. The WHO
SOLIDARITY trial includes a lopinavir‐ recommendation for or against says that clinicians should “not
ritonavir arm. The CDC states that tocilizumab due to insufficient routinely give systemic
“lopinavir‐ritonavir did not show evidence11. corticosteroids for the treatment of
promise for treatment of hospitalized viral pneumonia outside clinical
COVID‐19 patients with pneumonia in4. For hospitalized patients with trials.” The CDC says “corticosteroids
a recent clinical trial in China. This COVID‐19 who have evidence of should be avoided unless indicated
trial was underpowered…”. The FDA pneumonia, we make no suggestion for other reasons, such as
has not taken a position on the use of either for or against treatment with management of chronic obstructive
lopinavir‐ritonavir in COVID‐19. The systemic corticosteroids. 15% for pulmonary disease exacerbation or
Surviving Sepsis Campaign made a intervention, 18% no suggestion, and septic shock.” The FDA has not taken
weak recommendation against the 67% against intervention. a position on the use of systemic
routine use of lopinavir‐ritonavir11. corticosteroids in COVID‐19. The
Rationale for question. Patients Surviving Sepsis Campaign made a
For hospitalized patients with with COVID‐19 have elevated levels of weak recommendation against
COVID‐19 who have evidence of pro‐inflammatory cytokines and other systemic corticosteroids in
pneumonia, we make no suggestion inflammatory biomarkers20‐22, leading mechanically ventilated COVID‐19
either for or against treatment with some clinicians to postulate that patients without ARDS, but a weak
tocilizumab. 30% for intervention, systemic corticosteroid therapy may recommendation for systemic
56% no suggestion, and 14% against be beneficial. However, studies from corticosteroids in mechanically
intervention. patients with other viral infections ventilated COVID‐19 patients with
suggest that systemic corticosteroids ARDS11.
Rationale for question. Patients may confer no benefit or may have
with COVID‐19 have elevated levels of harmful effects, including increased 5. For patients with refractory
the pro‐inflammatory cytokine, IL‐6, viral replication and prolonged viral hypoxemia due to progressive
with the most severely ill patients shedding23‐26. COVID‐19 pneumonia (i.e., ARDS),
exhibiting the highest levels20‐22. Results. Sixty‐seven percent of the we suggest prone ventilation. 99%
Tocilizumab is an anti‐IL‐6 monoclonal task force favored a suggestion for intervention, 1% no suggestion,
antibody that has proven effective in against systemic corticosteroids for and 0% against intervention.
other IL‐6 mediated diseases. It is the treatment of COVID‐19. This was
recommended by China’s National only two votes shy of enough Refractory hypoxemia refers to an
agreement to make a consensus SpO2 consistently less than 90%
6 Updated April 3, 2020despite maximal ventilator 6. For patients with refractory The task force’s goal was to
interventions to increase the SpO2. hypoxemia due to progressive provide interim guidance for
COVID‐19 pneumonia (i.e., ARDS), therapeutic interventions to frontline
Rationale for question. Patients we suggest that extracorporeal clinicians, based upon scarce direct
with COVID‐19 may develop viral membrane oxygenation (ECMO) be evidence, indirect evidence, and the
pneumonia, which can progress to considered if prone ventilation fails. observations and experiences of
ARDS. Clinical practice guidelines 75% for intervention, 23% no other clinicians around the world who
make a strong recommendation for suggestion, and 1% against have battled COVID‐19, using a
prone ventilation for more than 12 intervention. consensus‐building process called the
hours in patients with severe ARDS28; CORE process1,2. The task force
however, prone ventilation has not Rationale for question. Patients suggests prone ventilation for COVID‐
been studied in COVID‐19 patients. with COVID‐19 may develop viral 19 patients with refractory
Results. The task force agreed that pneumonia, which can progress to hypoxemia, ECMO for COVID‐19
patients with refractory hypoxemia ARDS. Clinical practice guidelines patients with refractory hypoxemia
due to progressive COVID‐19 declined to make a recommendation who fail prone ventilation and, on a
pneumonia (i.e., ARDS) should for or against ECMO in ARDS28 and case‐by‐case basis,
undergo prone ventilation. This was ECMO has not been studied in COVID‐ hydroxychloroquine or chloroquine in
based upon the assumption that 19 patients. the context of shared decision‐
ARDS due to COVID‐19 behaves like Results. Seventy‐five percent of making, data collection for research,
ARDS due to other causes for which the task force agreed that patients severe enough disease to warrant
the benefits of prone ventilation are with refractory hypoxemia due to investigational therapy, and sufficient
well established. Agreement with the progressive COVID‐19 pneumonia quantities of drug are available
assumption of similarity was not (i.e., ARDS) should be considered for (Table).
universal, however, as several task ECMO; this was adequate agreement This interim guidance has several
force members argued that ARDS in for a consensus suggestion in favor of important limitations. There may
COVID‐19 is unique because lung ECMO. The task force emphasized have been selection bias during task
compliance is maintained and the that ECMO should be contemplated force composition, favoring those
effects of prone ventilation more only after failing prone ventilation. with professional connections with
modest than in typical ARDS, a view The task force acknowledged that the American Thoracic Society and,
supported by a recent research ECMO may not be feasible during therefore, pulmonary and critical care
29
letter . Nevertheless, the task force much of a pandemic because it is medicine. Since COVID‐19 is a new
concluded that prone ventilation is resource intensive, challenging from disease being managed by a variety of
worth a trial since it is low risk and an infection control perspective, and specialties ranging from intensivists
low cost. However, they warned that requires frequent blood transfusions to infectious disease specialists,
placing the patient in the prone at a time when blood may be in expertise in COVID‐19 management
position must be done with caution shortage. was probably variable across task
since there is a risk of transmitting What others are saying. The force members; this was enhanced by
infection to healthcare staff due to WHO, CDC, and FDA have not the inclusion of multiple specialties to
aerosolized secretions. addressed ECMO. The Surviving ensure that we have appropriate
What others are saying. The WHO, Sepsis Campaign made a weak expertise for future versions of the
CDC, and FDA have not addressed recommendation for veno‐venous guidance, which may include infection
prone ventilation. The Surviving ECMO or referral to an ECMO center control, radiological findings, and
Sepsis Campaign made a weak in patients with refractory hypoxemia other topics. The document did not
recommendation for prone despite recruitment maneuvers11. address the combination of
ventilation in patients with moderate hydroxychloroquine plus
to severe ARDS11. Discussion azithromycin, which is being used in
many institutions currently. Finally,
crude data was not collected in a
7 Updated April 3, 2020fashion that enabled comparison of In conclusion, empirical evidence, prevention. The suggestions provided
different groups of task force particularly randomized trials, are in this document will be periodically
members, such as North Americans desperately needed to guide therapy. reevaluated as new evidence emerges
versus Europeans, clinicians versus Supportive care remains the mainstay and modified accordingly.
thought leaders, etc. of treatment and social distancing
remains an important part of
Table‐ Interim Guidance on Management of COVID‐19
Vote from CORE process
Suggestions for
(>70% agreement to make suggestion)
For any COVID‐19 patient who receives an intervention suggested in this
document, data should be collected in a manner that enables studies that
use valid methods for causal inference and control of confounders. The data
No vote
should be assessed periodically so that patients who received the
intervention can be compared those who did not receive the intervention.
Management should be modified as‐needed based upon the comparisons.
Hydroxychloroquine (HCQ) or chloroquine (CQ) for patients with
confirmed COVID‐19 and severe pneumonia if:
Shared decision‐making is utilized, and 73% for HCQ or CQ
Data is collected for research comparing HCQ to no HCQ, or CQ to no 16% no suggestion
CQ, and 11% against HCQ or CQ
Illness is severe enough to warrant investigational therapy, and
HCQ or CQ are not in short supply.
99% for prone ventilation
Prone ventilation for patients with refractory hypoxemia due to progressive
1% no suggestion
COVID‐19 pneumonia (i.e., ARDS)
0% against prone ventilation
Consideration of ECMO for patients with refractory hypoxemia due to 75% for ECMO
progressive COVID‐19 pneumonia (i.e., ARDS) who have failed prone 23% no suggestion
ventilation 1% against ECMO
No suggestion for or against
18% for HCQ or CQ
HCQ or CQ for outpatient COVID‐19 patients 36% no suggestion
46% against HCQ or CQ
8% for HCQ or CQ
HCQ or CQ for hospitalized COVID‐19 patients without pneumonia 50% no suggestion
42% against HCQ or CQ
68% for remdesivir
Remdesivir for hospitalized COVID‐19 patients with pneumonia 26% no suggestion
5% against remdesivir
30% for lopinavir‐ritonavir
Lopinavir‐ritonavir for hospitalized COVID‐19 patients with pneumonia 26% no suggestion
43% against lopinavir‐ritonavir
30% for tocilizumab
Tocilizumab for hospitalized COVID‐19 patients with pneumonia 56% no suggestion
14% against tocilizumab
15% for intervention
Systemic corticosteroids for hospitalized COVID‐19 patients with pneumonia 18% no suggestion
67% against intervention
CORE= Convergence of Opinion on Recommendations and Evidence; ARDS= Acute Respiratory Distress Syndrome; ECMO=
Extracorporeal Membrane Oxygenation
8 Updated April 3, 2020International Task Force
Alan F. Barker Pulmonary and Critical Care USA‐ Oregon
Abigail Chua Pulmonary and Critical Care USA‐ New York
Jonathan H. Chung Radiology USA‐ Illinois
Gustavo Cortes‐Puentes Pulmonary and Critical Care USA‐ Minnesota
Kristina Crothers Pulmonary and Critical Care USA‐ Washington
Charles Delacruz Pulmonary and Critical Care USA‐ Connecticut
Sarah Doernberg Infectious Diseases USA‐ Northern California
Abhijit Duggal Pulmonary and Critical Care USA‐ Ohio
Michelle Gong Pulmonary and Critical Care USA‐ New York
Michael K. Gould Pulmonary and Critical Care USA‐ Southern California
Margaret Hayes Pulmonary and Critical Care USA‐ Massachusetts
Carolyn Hendrickson Pulmonary and Critical Care USA‐ Northern California
Steven Holets Respiratory Therapy USA‐ Minnesota
Catherine L. Hough Pulmonary and Critical Care USA‐ Washington
Michael H. Ieong Pulmonary and Critical Care USA‐ Massachusetts
Maximiliano Tamae‐Kakazu Pulmonary and Critical Care USA‐ Michigan
May M. Lee Pulmonary and Critical Care USA‐ Southern California
Janice Liebler Pulmonary and Critical Care USA‐ Southern California
John B. Lynch Infectious Diseases USA‐ Washington
Aneesh K. Mehta Infectious Diseases USA‐ Georgia
Ari Moskowitz Pulmonary and Critical Care USA‐ Massachusetts
Michael S. Niederman Pulmonary and Critical Care USA‐ New York
Richard Oeckler Pulmonary and Critical Care USA‐ Minnesota
Ganesh Raghu Pulmonary and Critical Care USA‐ Washington
Julio A. Ramirez Infectious Diseases USA‐ Kentucky
Noah C. Schoenberg Pulmonary and Critical Care USA‐ Massachusetts
Sugeet Jagpal Pulmonary and Critical Care USA‐ New Jersey
Charlie Strange Pulmonary and Critical Care USA‐ South Carolina
Francesca Torriani Infectious Diseases USA‐ Southern California
Allan Walkey Pulmonary and Critical Care USA‐ Massachusetts
Kevin C. Wilson Pulmonary and Critical Care USA‐ Massachusetts
Richard Wunderink Pulmonary and Critical Care USA‐ Illinois
Luca Richeldi Pulmonary Medicine Italy
Stefano Aliberti Pulmonary Medicine Italy
Enrico Storti Anesthesiology and Critical Care Italy
Tommaso Mauri Anesthesiology and Critical Care Italy
Mirko Belliato Anesthesiology and Critical Care Italy
Pierre‐Regis Burgel Pulmonary Medicine France
Martine Remy‐Jardin Radiology France
Antoni Torres Pulmonary Medicine Spain
Jordi Rello Pulmonary Medicine Spain
9 Updated April 3, 2020Miriam Barrecheguren Pulmonary Medicine Spain
Inigo Ojanguren Pulmonary Medicine Spain
Oriol Roca Critical Care Medicine Spain
Jordi Riera Critical Care Medicine Spain
Anthony O'Regan Pulmonary and Critical Care Ireland
Catherine Fleming Infectious Diseases Ireland
Andrew Menzies‐Gow Pulmonary Medicine England
James D. Chalmers Pulmonary Medicine Scotland
Mathias Pletz Infectious Diseases Germany
Elisabeth Bendstrup Pulmonary Medicine Denmark
Martina Vasakova Pulmonary Medicine Czech Republic
Wim Wuyts Pulmonary Medicine Belgium
Christopher J. Ryerson Pulmonary Medicine Canada
Christopher Carlsten Pulmonary and Occupational Medicine Canada
Lorenzo Delsorbo Critical Care Medicine Canada
James Johnston Pulmonary Medicine Canada
Ewan Goligher Critical Care Medicine Canada
Eddy Fan Pulmonary and Critical Care Canada
Janice Leung Pulmonary Medicine Canada
Tamera J. Corte Pulmonary Medicine Australia
Lauren K. Troy Pulmonary Medicine Australia
Grant Waterer Pulmonary Medicine Australia
Chin Kook (K.) Rhee Pulmonary Medicine South Korea
Gee‐Young Suh Pulmonary and Critical Care South Korea
Kyeongman Jeon Pulmonary and Critical Care South Korea
Doo Ryeon (R.) Chung Infectious Diseases South Korea
Yeon Wook (W.) Kim Pulmonary and Critical Care South Korea
Chunxue Bai Pulmonary Medicine China
Li Bai Pulmonary and Critical Care China
Tao Xu Pulmonary and Critical Care China
Dawei Yang Pulmonary and Critical Care China
Ziqiang Z. Zhang Pulmonary and Critical Care China
Xun Wang Pulmonary and Critical Care China
Sanjay H. Chotirmall Pulmonary and Critical Care Singapore
Ser Hon Puah Pulmonary and Critical Care Singapore
Takeshi Johkoh Radiology Japan
Hassan Chami Pulmonary and Critical Care Lebanon
Joaquin A. Zuniga Infectious Diseases Mexico
Carlos M. Luna Pulmonary Medicine Argentina
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