Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
Brief Summary: REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia.

The purpose of this study is to evaluate the effect of a range of interventions to improve outcome of patients admitted to intensive care with community-acquired pneumonia.

In addition, REMAP-CAP provides and adaptive research platform for evaluation of multiple treatment modalities in the event of a respiratory pandemic such as COVID-19.

REMAP-COVID is a sub-platform of REMAP-CAP that evaluates treatments specific to COVID-19 in the United States of America.


Options:
A: Inclusion Criteria:

1. Patients included in the CORIMUNO-19 cohort
2. Patients belonging to one of the 2 following groups:

   * Group 1: patients not requiring ICU at admission with moderate and severe pneumopathy according to the OMS Criteria of severity of COVID pneumopathy.

Moderate cases :

Cases meeting all of the following criteria:

* Showing fever and respiratory symptoms with radiological findings of pneumonia.
* Requiring between 3L/min and 5L/min of oxygen to maintain SpO2 \>97% Severe cases

Cases meeting any of the following criteria:

* Respiratory distress (≧30 breaths/ min);
* Oxygen saturation≤93% at rest in ambient air; or Oxygen saturation ≤97 % with O2 \> 5L/min.
* PaO2/FiO2≦300mmHg
* Group 2: patients requiring ICU based on Criteria of severity of COVID pneumopathy.
* Respiratory failure and requiring mechanical ventilation
* No do-not-resuscitate order (DNR order)

Exclusion Criteria:

* Patients with exclusion criteria to the CORIMUNO-19 cohort.
* Known hypersensitivity to Sarilumab or to any of their excipients.
* Pregnancy
* Current documented bacterial infection
* Patient with any of following laboratory results out of the ranges detailed below at screening should be discussed depending of the medication:
* Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
* Haemoglobin level: no limitation
* Platelets (PLT) \< 50 G /L
* SGOT or SGPT \> 5N
B: Inclusion criteria:

Subjects who meet all of the following criteria will be eligible to participate in the study:

1. Must have provided informed consent in a manner approved by the Investigator's Institutional Review Board (IRB) or Independent Ethics Committee (IEC) prior to any assessments. If a patient is unable to provide informed consent due to their medical condition, the patient's legally authorized representative may consent on behalf of the study patient, as permitted by local law and institutional Standard Operating Procedures;
2. Age Range: 19-85 years old
3. Male or female gender
4. Confirmed SARS-CoV-2 infection by nasopharyngeal swab PCR or serum assay for IgM antibody
5. Requiring hospital but not mechanical ventilation
6. Oxygen supplementation not greater than 10L delivered by any device
7. WITH evidence of severe COVID-19 (at least 2 of the following):

   1. Fever \> 38C within 72 hours
   2. Pulmonary infiltrate on CXR
   3. Need for supplemental O2 to maintain saturation \> 92%
8. AND at least 1 of the following:

   1. Ferritin \> 500 ng/ml
   2. CRP \> 50 mg/L
   3. LDH \>250 U/L
   4. D-dimer \> 1000 ng/mL
9. Women of childbearing potential (ie, not post-menopausal or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test before randomization. Participating women of childbearing potential must be willing to consistently use effective methods of contraception (ie, condom, combined oral contraceptive, implant, injectable, indwelling intrauterine device, or a vasectomized partner) from screening until at least 90 days after administration of the last dose of study drug;
10. The subject must be willing and able to provide informed consent and abide all study requirements and restrictions.

Exclusion criteria:

Subjects who meet any of the following criteria will be excluded from participation in the study:

1. Unable to provide verbal informed consent or have verbal agreement to participate through attestation and signature of a Witness required, as outlined in the Partners IRB's Table for Consenting in COVID Research that is More than Minimal Risk.
2. Subjects between the ages of 79 and 86 will be excluded if they have NYHA Class III/IV heart failure, insulin-dependent diabetes mellitus, angina, or treatment of a malignancy (excluding non-melanoma skin cancer) within six months
3. Uncontrolled bacterial, fungal, or non-COVID viral infection
4. Active TB
5. Any prior investigational immunosuppressive therapy within 28-days or 3 half-lives of the agent (for instance with biologic or JAK inhibitor)
6. Any concurrent immunosuppressive medication that the PI believes would put the patient at higher risk
7. Receipt of intravenous tocilizumab for the treatment of a non-COVID condition within three weeks of the first COVID symptom
8. History of hypersensitivity to tocilizumab
9. Any concurrent immunosuppressive medication that the PI believes would put the patient at higher risk
10. Treatment with other biologic or small-molecule immunosuppressive therapy such as IL1R-antagonism, JAK inhibition, or other agents
11. Treatment with convalescent plasma
12. History of diverticulitis or bowel perforation
13. ANC \<500, Platelets \<50,000\*
14. AST/ALT \> 5X ULN
15. Women who are pregnant or planning to get pregnant in the next 90 days;
16. Any condition that could interfere with, or for Known allergy to the study drug or any of its ingredients or known allergy to any other anti IL 6 agents;
17. Any condition that could interfere with or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would, in the opinion of the Investigator, increase the risk of the subject by participating in the study.

We note that anti-viral therapies may be administered to subjects if given in the context of a clinical trial. Nitric oxide treatment is also permitted at the discretion of the care team, ideally in the context of a clinical trial. Co-treatment chloroquine, hydroxychloroquine, and/or azithromycin is permitted for subjects in this protocol.
C: REMAP-CAP PLATFORM INCLUSION CRITERIA:

1. Adult patient admitted to an ICU for severe CAP within 48 hours of hospital admission with:

   1. symptoms or signs or both that are consistent with lower respiratory tract infection AND
   2. Radiological evidence of new onset consolidation (in patients with pre-existing radiological changes, evidence of new infiltrate)
2. Up to 48 hours after ICU admission, receiving organ support with one or more of:

   1. Non-invasive or Invasive ventilatory support;
   2. Receiving infusion of vasopressor or inotropes or both

PLATFORM EXCLUSION CRITERIA:

1. Healthcare-associated pneumonia:

   1. Prior to this illness, is known to have been an inpatient in any healthcare facility within the last 30 days
   2. Resident of a nursing home or long term care facility
2. Death is deemed to be imminent and inevitable during the next 24 hours AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment
3. Previous participation in this REMAP within the last 90 days

REMAP-COVID PLATFORM INCLUSION CRITERIA

1. Adult patients (≥ 18 years) admitted to hospital with acute illness due to suspected or proven pandemic infection.

REMAP-COVID PLATFORM EXCLUSION CRITERIA

1. Death is deemed to be imminent and inevitable during the next 24 hours AND one or more of the patient, substitute decision maker or attending physician are not committed to full active treatment
2. Patient is expected to be discharged from hospital today or tomorrow
3. More than 14 days have elapsed while admitted to hospital with symptoms of an acute illness due to suspected or proven pandemic infection.
4. Previous participation in this REMAP within the last 90 days

DOMAIN-SPECIFIC ELIGIBLE CRITERIA:

Each domain may have additional eligibility criteria. Refer to the study website for more information (www.remapcap.org).
D: Inclusion Criteria:

* Recent ( ≥ 6 days of flu-like symptoms or malaise yet ≤16 days of flu-like symptoms or malaise prior to randomization) infection with COVID-19.
* Confident COVID-19 diagnosis confirmed by antigen detection test and/or PCR and/or positive serology, or any emerging and validated diagnostic laboratory test for COVID-19 within this period.
* In some patients, it may be impossible to get a confident laboratory confirmation of COVID-19 diagnosis after 24h of hospital admission because viral load is low and/or problems with diagnostic sensitivity. In those cases, in absence of an alternative diagnosis, and with highly suspect bilateral ground glass opacities on recent (\<24h) chest-CT scan (confirmed by a radiologist and pulmonary physician as probable COVID-19), and a typical clinical and chemical diagnosis with signs of cytokine release syndrome, a patient can be enrolled as probable COVID-19 infected. In all cases, this needs confirmation by later seroconversion.
* Presence of hypoxia defined as PaO2/FiO2 below 350 while breathing room air in upright position or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation
* signs of cytokine release syndrome defined as ANY of the following:

  1. serum ferritin concentration \>1000 mcg/L and rising since last 24h
  2. single ferritin above 2000 mcg/L in patients requiring immediate high flow oxygen device or mechanical ventilation
  3. lymphopenia defined as \<800 lymphocytes/microliter) and two of the following extra criteria

     * Ferritin \> 700 mcg/L and rising since last 24h
     * increased LDH (above 300 IU/L) and rising last 24h
     * D-Dimers \> 1000 ng/mL and rising since last 24h
     * CRP above 70mg/L and rising since last 24h and absence of bacterial infection
     * if three of the above are present at admission, no need to document 24h rise
* Chest X-ray or CT scan showing bilateral infiltrates within last 2 days
* Admitted to specialized COVID-19 ward or an ICU ward taking care of COVID-19 patients
* Age ≥ 18yrs
* Male or Female
* Willing and able to provide informed consent or legal representative willing to provide informed consent

Exclusion Criteria:

* Patients with known history of serious allergic reactions, including anaphylaxis, to any of the study medications, or any component of the product.
* mechanical ventilation \> 24 h at Randomization
* Patient on ECMO at time of screening
* clinical frailty scale above 3 (This frailty score is the patient status before first symptoms of COVID-19 episode.)
* active bacterial or fungal infection
* unlikely to survive beyond 48h
* neutrophil count below 1500 cells/microliter
* platelets below 50.000/microliter
* Patients enrolled in another investigational drug study
* patients on high dose systemic steroids (\> 20 mg methylprednisolone or equivalent) for COVID-19 unrelated disorder
* patients on immunosuppressant or immunomodulatory drugs
* patients on current anti-IL1 or anti-IL6 treatment
* signs of active tuberculosis
* serum transaminase levels \>5 times upper limit of normal
* bowel perforation or diverticulitis
* pregnant or breastfeeding females (all female subjects deemed of childbearing potential by the investigator must have negative pregnancy test at screening)
* Women of childbearing potential must have a negative serum pregnancy test pre-dose on day 1. Woùmen of childbearing potential must consistently and correctly use (during the entire treatment period and 3 months after last reatment) 1 highly effective method for contraception.

Answer: C