Treatments for outpatients with mild-to-moderate COVID-19 are available at BILH. These drugs are also available at state-run facilities and commercial pharmacies. We strongly encourage providers to treat or refer at-risk ambulatory patients with mild-to-moderate COVID-19 as soon as they are eligible for treatment.

The following materials are designed to provide BILH clinicians and staff with the information you need to treat or refer patients for the available COVID-19 outpatient therapies. This toolkit also includes the key points for patient counseling and details on the process for therapy allocation in the setting of a shortage of all available options for treatment.

Treatment Guidelines

Treatment of Mild-Moderate Infection in the Outpatient Setting

  • As of April 2022, our available outpatient therapies for the treatment of COVID-19 include:
    • Nirmatrelvir co-packaged with ritonavir (Paxlovid) – Emergency Use Authorization
    • Remdesivir – FDA Approved
    • Monoclonal antibody therapy (bebtelovimab) – Emergency Use Authorization
  • The monoclonal antibody therapy sotrovimab is no longer available in any setting after its EUA was revoked by the FDA 4/2022 in response to the prevalence of new variants.
  • The decision regarding optimal treatment is based on efficacy, safety, logistical constraints, and patient specific factors.
    • BILH has released updated treatment guidelines for mild-moderate COVID-19 that prioritize the oral drug nirmatrelvir with ritonavir (Paxlovid) as the preferred drug, followed by intravenous remdesivir for those unable to receive nirmatrelvir with ritonavir (Paxlovid). This approach concurs with guidance from Massachusetts DPH and NIH.
    • Nirmatrelvir with ritonavir (Paxlovid) may only be used within the first five days of symptom onset (date of symptom onset = day 0), thus early referral is critical.
      • The referring provider is responsible for screening for contraindications due to the potential for significant drug-drug interactions.
      • Providers should directly prescribe nirmatrelvir with ritonavir (Paxlovid) to a BILH Outpatient Pharmacy or select retail pharmacies. Prescription of nirmatrelvir with ritonavir (Paxlovid) does not require use of the BILH COVID-19 Outpatient Therapeutics Referral Form.
      • Please see the following for additional details:
    • For patients who are unable to receive nirmatrelvir with ritonavir (Paxlovid), remdesivir may be given up to seven days from symptom onset. Unlike nirmatrelvir/ritonavir (Paxlovid) and bebtelovimab that are available through emergency use authorization (EUA), remdesivir has full FDA approval. Use of this agent for outpatients may be limited by the need for three daily consecutive intravenous infusions and ongoing infusion capacity limitations, but it is preferred over bebtelovimab.
    • Monoclonal antibody therapy, i.e., bebtelovimab, may be given within the first seven days of symptom onset, and is reserved for patients unable to take nirmatrelvir with ritonavir (Paxlovid) or remdesivir, either due to contraindications or resource limitations, as use of bebtelovimab is supported by relatively limited evidence of safety and efficacy.
    • The order of preference for these drugs is not altered for individuals who are pregnant, but such individuals should review their options with their obstetric providers.
    • Providers should directly prescribe nirmatrelvir with ritonavir (Paxlovid) to a BILH Outpatient Pharmacy or select retail pharmacies. For IV remdesivir or bebtelovimab, providers can initiate a request for all available treatments by completing the BILH COVID-19 Therapeutics referral form.
    • Prescribers may also refer patients to COVID Therapeutics sites offered by Massachusetts Department of Public Health and run by Gothams (referral form).
    • In settings of drug shortage, the BILH COVID-19 Therapeutics Drug Shortage Task Force has approved a treatment allocation guideline based on prioritizing those patients most likely to receive the greatest benefit from therapy.
  • Treatments are now available for outpatients with mild-to-moderate COVID-19.
  • You will be considered for all available COVID-19 therapeutics.
  • If supplies become limited at any time, your health conditions, age and vaccination status will be used to determine your eligibility for treatment so that we can prioritize those individuals most likely to benefit.
    • Nirmatrelvir with ritonavir (Paxlovid) is an available oral antiviral medicine that must be used within the first five days of symptom onset. Nirmatrelvir with ritonavir (Paxlovid) will be preferred when available and when there are no contraindications. We will screen to make sure you don’t have any medications that can interact or health conditions that would prevent you from using it.
    • Remdesivir, an anti-viral treatment, is given intravenously by infusion at an outpatient infusion center and must be used within seven days of symptom onset. Remdesivir is given in three doses over the course of three consecutive days. All three doses must be administered for this medication to be effective.
    • Monoclonal antibody treatment given intravenously by infusion at an outpatient infusion center may be used within seven days of symptom onset and is given as a single dose in one visit.
    • Remdesivir has full FDA approval. Nirmatrelvir with ritonavir (Paxlovid) and bebtelovimab are under emergency use authorization (EUA).
    • Bebtelovimab is reserved for patients who cannot receive the other treatments because there is more limited evidence of safety and efficacy for this medication.
    • The order of preference for these drugs is the same for individuals who are pregnant, but such individuals should review their options with their obstetric providers.
  • If we experience future supply shortages, your provider may pursue options for treatment at the COVID Therapeutics sites offered by Massachusetts Department of Public Health.
  1. Confirm patient eligibility:
    1. Only patients with symptomatic COVID-19 with symptom onset and a positive PCR or antigen test within the past seven days are eligible. Date of symptom onset = Day 0.
    2. Patients MUST have at least one risk factor for progression to severe COVID-19.
    3. Providers should directly prescribe nirmatrelvir with ritonavir (Paxlovid) to a BILH Outpatient Pharmacy (please include date of symptom onset in the prescription) or select retail pharmacies. Prescription of nirmatrelvir with ritonavir (Paxlovid) does not require use of the BILH COVID-19 Outpatient Therapeutics Referral Form.
  2. For patients unable to receive nirmatrelvir with ritonavir (Paxlovid), submit a referral through the BILH COVID-19 Therapeutics Referral Form:
    1. It is very important that the form is completed fully and accurately to inform allocation of treatment.
    2. Please verify the provider contact information prior to submission as incorrect email addresses may delay your patient’s consideration for treatment.
      1. Practices may consider use of a single, common or frequently checked email address to coordinate all referrals with the COVID-19 Therapeutics team. We are unable to accept multiple emails.
  3. Submit an order for COVID-19 mAb therapy in your BILH Electronic Health Record (if applicable)
    1. Epic access through Lahey Hospital & Medical Center and legacy Lahey sites – complete a referral order for COVID-19 mAb therapy in Epic
    2. WebOMR providers – complete an order for COVID-19 mAb therapy in the WebOMR infusion tab
  4. All other providers – no further action needed at the time of referral. Check your email for the following COVID-19 therapeutics communications:
    1. Confirmation that referral has been received – all electronic referrals will receive a confirmation email from [email protected] – if this is not received within 15 minutes, please resubmit and check the email address used for submission. Incorrectly entered email addresses are the most common cause of lack of receipt of notifications.
    2. Scheduling for remdesivir or COVID-19 monoclonal antibody therapy – you will only receive a notice if the patient has been allocated a treatment slot at one of our treatment sites.
    3. COVID-19 Therapeutics Declined – you will be notified if we are unable to allocate any treatments to your patient due to limited infusion capacity or drug supplies.
  • Your health and safety are our top priority, and we are committed to the safe, equitable distribution of COVID-19 therapeutics.
  • Several therapeutic treatments are now available for outpatients with mild-to-moderate COVID-19.
  • We are offering COVID-19 oral antiviral treatment with nirmatrelvir co-packaged with ritonavir (Paxlovid) through our BILH outpatient pharmacies and this is also available at select retail pharmacies. While oral treatments are more convenient, these medications may not be right for everyone, and your health provider will determine if they are right for you. This includes ensuring there are no potential medication interactions and reviewing the side effects with you prior to prescribing.
  • For patients who can’t receive nirmatrelvir co-packaged with ritonavir (Paxlovid), we are offering intravenous remdesivir as a second option, and lastly COVID-19 monoclonal antibody therapy (bebtelovimab) at BIDMC and LHMC.
  • We are committed to keeping you informed as BILH and the state continue to expand access to COVID-19 therapeutics.
  • If you have an opportunity to receive treatment elsewhere before it is available to you at Beth Israel Lahey Health, we encourage you to seek treatment if you qualify as soon as possible.

Provider COVID-19 Therapeutics FAQs

What are the current treatment options?
  • Nirmatrelvir co-packaged with ritonavir (Paxlovid)
  • Remdesivir
  • Monoclonal antibody therapy (i.e., bebtelovimab)
Are any of these therapies preferred over another?
  • The decision regarding optimal treatment is based on efficacy, safety, logistical constraints, and patient specific factors.
  • BILH has released updated treatment guidelines for mild-moderate COVID-19 that prioritize the oral drug nirmatrelvir with ritonavir (Paxlovid) as the preferred drug, followed by intravenous remdesivir for those unable to receive nirmatrelvir with ritonavir (Paxlovid).
  • The monoclonal antibody therapy sotrovimab is no longer available in any setting after its EUA was revoked by the FDA in 4/2022 in response to the prevalence of new variants.
  • The oral antiviral therapies may only be used within the first five days of symptom onset (date of symptom onset = day 0), thus early referral is critical.
    • The referring provider is responsible for screening for contraindications due to the potential for significant drug-drug interactions.
    • Please see the following for additional details:
    • The order of preference for these drugs is not altered for individuals who are pregnant, but such individuals should review their options with their obstetric providers.
    • For individuals referred between 6-7 days of symptom onset, remdesivir and monoclonal antibody e.g. bebtelovimab are the only options for therapy.
    • Use of remdesivir requires three daily intravenous infusions and use may be contingent upon ongoing infusion capacity limitations.
Where are Remdesivir and COVID-19 Monoclonal Antibody Treatments offered?
  • Beth Israel Deaconess Medical Center (BIDMC)
  • Lahey Hospital & Medical Center (LHMC)
How will oral antiviral therapies be distributed?
  • Providers can directly prescribe nirmatrelvir with ritonavir (Paxlovid) to a BILH Outpatient Pharmacy or select retail pharmacies.
  • For IV remdesivir or bebtelovimab initiate a request for available treatments by completing the BILH COVID-19 Outpatient Therapeutics Referral Form.
    • Once treatment is allocated by the BILH COVID-19 Therapeutics team, referring providers will be contacted.
How are patients prioritized for treatment?
  • At present, COVID-19 treatments are not in shortage.
  • In settings of shortage, the BILH COVID-19 Therapeutics Drug Shortage Task Force has approved a treatment allocation guideline based on prioritizing those patients most likely to receive the greatest benefit from therapy.
  • Patients with severe immunosuppression will be prioritized followed by those who are unvaccinated with priority based on age ≥75, followed by vaccinated individuals with priority based on age ≥75. Tiers will then be further prioritized based on additional risk factors including BMI ≥ 35, moderate immunosuppression, not up to date on COVID-19 vaccine (i.e., unboosted), pregnancy and social vulnerability index.
How is COVID-19 vaccination primary series defined?
  • Completion of a primary vaccine series (defined as either 2-doses of a mRNA vaccine (Pfizer or Moderna) or 1-dose of J&J vaccine >14 days prior to referral
Why are you collecting data on race & ethnicity?
  • As of January 24, 2022 we are utilizing The CDC/ATSDR social vulnerability index (SVI) in our allocation scheme to help ensure equity of distribution of therapeutics. SVI uses 15 US census variables to help identify communities at higher risk of suffering potential negative effects caused by external stresses on health. We are collecting data on race and ethnicity as part of required reporting for the MA Department of Public Health. In addition, race and ethnicity may be a qualifying criterion for eligibility for treatment when associated with a higher risk of hospitalization or death from COVID-19, including Black or African American, Hispanic or Latinx, American Indian or Alaska Native.
How is severe immunosuppression categorized?
  • Hematologic malignancy meeting the following criteria:
    • Chimeric antigen receptor T cell (CAR-T) recipients (any history)
    • History of hematopoietic cell transplant within 1 year
    • Patients with hematologic malignancies who are on active therapy
    • Patients receiving Bruton tyrosine kinase inhibitors
    • Post-hematopoietic cell transplant recipients who have chronic graft versus host disease or who are taking immunosuppressive medications
  • Within 1 year of receiving B-cell depleting therapies (e.g., rituximab, ocrelizumab, ofatumumab, alemtuzumab)
  • Severe combined immunodeficiencies (SCID)
  • Untreated HIV with CD4 T lymphocyte cell count <50 cells/mm3
  • Solid organ transplantation meeting the following criteria:
    • History of lung transplant at any time
    • Patients with a history of solid organ transplant within 1 year
      • Treatment for acute rejection with T or B cell depleting agents within 6 months
How is moderate immunosuppression categorized?
  • Active systemic treatment with any of the following:
    • Alkylating agents (e.g., cyclophosphamide)
    • Antimetabolites (e.g., azathioprine, methotrexate)
    • JAK inhibitors
    • Medium to high-dose corticosteroids (>=10mg prednisone or equivalent daily for greater than 2 consecutive weeks)
    • TNF blockers (e.g. etanercept, adalimumab, infliximab)
    • Transplant-related immunosuppressive drugs (e.g., cyclosporine, tacrolimus, azathioprine, mycophenolate)
  • Advanced (CD4 51-200 or presence of AIDS-defining illness) or untreated HIV infection
  • History of hematologic cell transplant >1 year prior and not requiring any immunosuppressive therapies
  • History of solid organ transplant > 1 year prior (excluding lung) and patient is taking immunosuppressive therapy
  • Moderate or severe primary immunodeficiencies (e.g. DiGeorge syndrome, Wiskott-Aldrich, Common Variable Immunodeficiency or hypogammaglobulinemia requiring immunoglobulin therapy)
  • Solid tumor with last treatment within 3 months or remission has not been achieved
What are the other risk factors for progression to severe COVID-19?
  • All other immunosuppressive medications not classified as moderate or severe
  • Asplenia or functional asplenia
  • Autoimmune disease requiring ongoing systemic therapy
  • High Risk Body-Mass Index (BMI):
    • 25-30 kg/m2 AND not fully vaccinated with primary 1-2 dose series (no vaccination or series completed less than 2 weeks prior)
    • >30 kg/m2 regardless of vaccination status
  • Cardiovascular disease or hypertension
  • Chronic kidney disease
  • Chronic liver disease
  • Chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension)
  • Diabetes
  • Having a medical-related technological dependence (e.g. tracheostomy, gastrostomy, or positive pressure ventilation [not related to COVID 19])
  • HIV with CD4 >200
  • Neurodevelopmental disorders (e.g. cerebral palsy, genetic/metabolic syndromes severe congenital anomalies)
  • Primary immunodeficiency not listed as moderate or severe
  • Race/ethnicity that is associated with a higher risk of hospitalization or death from COVID-19, including Black or African American, Hispanic or Latinx, American Indian or Alaska Native
  • Sickle cell disease or other hemoglobinopathy
  • Treatment with interleukin inhibitors (IL12, 17, 23 etc.)
How is the order of therapy allocation determined?
  • For most ambulatory patients within five days of symptom onset (date of symptom onset = day 0), nirmatrelvir co-packaged with ritonavir (Paxlovid) will be the preferred treatment.
    • Screening for contraindications due to the potential for significant drug-drug interactions is required.
  • The order of preference for these drugs is not altered for individuals who are pregnant, but such individuals should review their options with their obstetric providers.
  • For individuals referred between 6-7 days of symptom onset and those unable to take nirmatrelvir co-packaged with ritonavir (Paxlovid), remdesivir is the recommended treatment.
  • For individuals referred between 6-7 days of symptom onset and those unable to take nirmatrelvir co-packaged with ritonavir (Paxlovid) or receive remdesivir, a monoclonal antibody (i.e., bebtelovimab) is the only option for therapy at this time.
    • Bebtelovimab is reserved for patients unable to take other options due to relatively limited evidence of safety and efficacy.
How is the BILH COVID-19 IV remdesivir and monoclonal antibody therapy location determined?
  • Our first priority is to offer treatment slots in an equitable fashion based on patient prioritization. Within eligible groups of patients, we then do our best to schedule based on geographic factors including where the patient lives and proximity to the referring provider. Unfortunately, given limited slots available, it is not always feasible for us to accommodate patient preference for treatment location.
How will my patient be informed of a treatment slot?
  • Once a treatment slot is allocated, a BILH COVID-19 treatment site will reach out to the patient directly to schedule. Once complete, you will receive a confirmation email.
How will I know if my patient is allocated a treatment course with a COVID-19 oral antiviral therapy?
  • Providers should directly prescribe nirmatrelvir with ritonavir (Paxlovid) to a BILH Outpatient Pharmacy or select retail pharmacies. Prescription of nirmatrelvir with ritonavir (Paxlovid) does not require use of the BILH COVID-19 Outpatient Therapeutics Referral Form. Prescriptions must be picked up from BILH pharmacies by a patient’s family member or designee (unless exceptional circumstances).
How is nirmatrelvir co-packaged with ritonavir (Paxlovid) Dosed/Supplied?
  • Authorized Dose: Two 150mg tablets (300mg) nirmatrelvir and with One 100mg tablet ritonavir orally BID x 5 days
  • Each carton contains five blister packs, one for each day
  • Dose reduction is needed for moderate renal impairment
How is nirmatrelvir co-packaged with ritonavir (Paxlovid) prescribed?
What drug interactions are considered for nirmatrelvir co-packaged with ritonavir (Paxlovid)?
Can patients with renal impairment take nirmatrelvir co-packaged with ritonavir (Paxlovid)?
  • Individuals with moderate renal impairment require dose adjustment. Use of nirmatrelvir co-packaged with ritonavir is not recommended for those with severe renal impairment (<30 mL/min).
  • Please see the table below for details on renal dose adjustment
eGFR Nirmatrelvir co-packaged with Ritonavir Dose
>60 mL/min 300 mg nirmatrelvir with 100 mg ritonavir, taken twice daily for 5 days
≥30 to ≤60 ml/min (moderate renal impairment) 150 mg nirmatrelvir with 100 mg ritonavir, taken twice daily for 5 days
<30 mL/min (severe renal impairment) Not recommended
Can nirmatrelvir co-packaged with ritonavir (Paxlovid) be used in individuals who are pregnant, lactating or with child-bearing potential?
  • There are no available human data on the use of nirmatrelvir during pregnancy.  Other protease inhibitors (darunavir and atazanavir), boosted with ritonavir, are among the first-line recommended treatment for pregnant people living with HIV and no increased risk of congenital abnormalities or adverse maternal or fetal outcomes have been noted. Use with appropriate caution in pregnancy as data is limited.
  • There are no specific recommendations for birth control in individuals with childbearing potential.
  • Breast feeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing infant to COVID-19.
Use of nirmatrelvir co-packaged with ritonavir (Paxlovid) in other populations:
  • Nirmatrelvir with ritonavir (Paxlovid) is not recommended for patients who have severe hepatic impairment (Child-Pugh Class C)
  • In patients with uncontrolled or undiagnosed HIV infection, there is a risk of selection for resistance to HIV protease inhibitors because nirmatrelvir is co-administered with ritonavir.