Special Considerations in People Who Are Immunocompromised
Last Updated: July 21, 2023
Prevention of COVID-19
Management of Patients With COVID-19 Who Are Immunocompromised
|Each recommendation in the Guidelines receives a rating for the strength of the recommendation (A, B, or C) and a rating for the evidence that supports it (I, IIa, IIb, or III). See Guidelines Development for more information.|
Approximately 3% of people in the United States have immunocompromising conditions.1 People who are immunocompromised are a heterogeneous population, and the severity of COVID-19 can vary significantly in this group. Some individuals who are immunocompromised may have a higher risk of hospitalization, complications, or death, and some may have outcomes that are comparable to those in the general population.
This section pertains to people who are moderately or severely immunocompromised, which includes those who:
- Are receiving active treatment for solid tumor and hematologic malignancies.
- Have hematologic malignancies (e.g., chronic lymphocytic lymphoma, non-Hodgkin lymphoma, multiple myeloma, acute leukemia) and are known to have poor responses to COVID-19 vaccines or an increased risk of severe COVID-19, regardless of the treatment status for the hematologic malignancy.
- Received a solid-organ or islet transplant and are receiving immunosuppressive therapy.
- Received chimeric antigen receptor T cell (CAR T-cell) therapy or a hematopoietic cell transplant (HCT) and are within 2 years of transplantation or are receiving immunosuppressive therapy.
- Have a moderate or severe primary immunodeficiency (e.g., severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome, common variable immunodeficiency disease).
- Have advanced or untreated HIV infection (defined as people with HIV and CD4 T lymphocyte [CD4] cell counts <200 cells/mm3, a history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV).
- Are receiving active treatment with high-dose corticosteroids (i.e., ≥20 mg prednisone or equivalent per day when administered for ≥2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, or immunosuppressive or immunomodulatory biologic agents (e.g., B cell–depleting agents).
Analyses have found a higher risk of hospitalization or death from COVID-19 in those with a variety of immunocompromising conditions, including rheumatic diseases, hematological malignancies, solid organ transplants, and HIV.2-7 Factors that increase the risk of severe COVID-19 in the general population, such as older age, chronic kidney disease, cardiovascular disease, and other comorbidities, are significant drivers of risk in people who are immunocompromised. Moreover, some immunodeficiencies seem to increase the risk above and beyond traditional risk factors. For example, there is evidence that individuals who make autoantibodies to type I interferons (proteins that are critical to the protective immune response against viral infections) have a higher risk of severe COVID-19.8 Similarly, certain classes of medications, such as T cell–depleting or T cell–suppressing agents (e.g., antithymocyte globulin, calcineurin inhibitors, mycophenolate mofetil, belatacept) and B cell–depleting agents (e.g., rituximab, ocrelizumab, obinutuzumab), have been associated with more severe disease.9,10
Prolonged shedding of SARS-CoV-2 has been reported in patients who are immunocompromised. A systematic review found that replication-competent virus could be detected for a median of 20 days in these patients, compared to 11 days in the general population.11 Prolonged viral shedding may affect SARS-CoV-2 testing strategies and isolation durations for this group of patients. Moreover, case reports suggest that prolonged infections can create evolutionary pressure for the emergence of variants that resist therapies or evade vaccine-induced immunity.12-14
For any person who is eligible, clinicians should prescribe therapies for the treatment of COVID-19 as recommended in these Guidelines. However, at times during the pandemic, logistical constraints have limited the availability of therapies. In those cases, the COVID-19 Treatment Guidelines Panel (the Panel) suggests prioritizing the treatment of patients with COVID-19 who are at the highest risk of clinical progression (see Prioritization of Anti-SARS-CoV-2 Therapies for the Treatment of COVID-19 in Nonhospitalized Patients When There Are Logistical Constraints). Providers should use their clinical judgment when prioritizing patients for treatment and assess a patient’s immunocompromised status, age, comorbidities, and vaccination status.
The sections below outline the Panel’s rationale for the recommendations on preventing and managing COVID-19 in people who are immunocompromised. Some of the special considerations for patients who are immunocompromised include the timing of COVID-19 vaccination, the management of immunosuppressive medications, and the strategies for treating COVID-19.
Prevention of COVID-19
COVID-19 vaccination remains the most effective way to prevent serious outcomes and death from SARS-CoV-2 infection. The Panel recommends COVID-19 vaccination for everyone who is eligible according to the guidance from the Centers for Disease Control and Prevention (CDC) (AI). This recommendation applies to:
- People who are moderately or severely immunocompromised
- People with active cancer and those receiving treatment for cancer
- Transplant and cellular immunotherapy candidates and recipients
- People with HIV
- All potential organ and hematopoietic cell donors
- Household members, close contacts, and health care workers who provide care for immunocompromised patients
Authorized and approved COVID-19 vaccines in the United States are not live-virus vaccines and can be safely administered to patients who are immunocompromised. However, in people who are immunocompromised, the immune response to vaccination may be blunted, and the timing of vaccination requires special consideration. Nevertheless, vaccination with a primary series and booster doses is still recommended, as it may confer partial protection, including protection from vaccine-induced, cell-mediated immunity.15
The Panel recommends following the current COVID-19 vaccination guidance from the CDC for people who are moderately or severely immunocompromised. This guidance only includes the use of the bivalent vaccines (which target the original SARS-CoV-2 virus strain plus the Omicron subvariants BA.4 and BA.5) and allows for additional doses in high-risk groups, including people aged >65 years and people with immunocompromising conditions.16,17 There is a lack of data on the optimal timing for repeat vaccination in people who are immunocompromised, and the CDC recommends an interval of at least 2 months after the last dose. Other considerations may include the patient's current or expected level of immunosuppression, their age, comorbidities, and the time since their last vaccine dose. Clinicians should also take into account the prevalence of SARS-CoV-2 infection in the community and whether the patient intends to travel.
A preprint of a large observational study from Israel suggests a potential benefit of administering COVID-19 boosters every 6 months in groups with the highest risk of COVID-19–related hospitalization or death.18 The CDC-funded VISION Network evaluated the effectiveness of bivalent vaccines between September 13, 2022, and April 21, 2023, at 5 sites in 7 states.19 Among adults who were immunocompromised, a lower vaccine effectiveness (VE) was observed for the bivalent booster, but VE was sustained against critical COVID-19–associated outcomes, including intensive care unit (ICU) admission and death. VE against hospitalization was 28% during the first 7 to 59 days after receipt of the bivalent dose and declined to 13% by 120 to 179 days; this indirectly supports using a 6-month interval for repeat vaccination.
The pivotal clinical trials that evaluated the safety and efficacy of the COVID-19 vaccines excluded people who were severely immunocompromised; therefore, the data for this population are less robust.20,21 Observational data suggest that serological responses to vaccines may be blunted in patients who are immunocompromised.22,23 However, a preprint of the MELODY trial reported detectable immunoglobulin G spike protein antibodies in approximately 80% of people in a large cohort of individuals in the United Kingdom who were immunocompromised and had received at least 3 doses of COVID-19 vaccines.24 Those who received anti-CD20 therapies within the past year had the lowest prevalence of detectable anti-spike protein antibodies.
Vaccination of Close Contacts
Clinicians should strongly encourage all household members and close contacts of patients who are immunocompromised to be vaccinated against COVID-19 as soon as possible (AI). Before Omicron became the dominant circulating variant, COVID-19 vaccines were shown to be associated with a reduction in SARS-CoV-2 infections not only among vaccinated individuals but also among unvaccinated adult household members in a large cohort study of health care workers in Finland.25 A 2022 systematic review and meta-analysis of 96 studies reported that people who received a complete primary COVID-19 vaccine series had reduced susceptibility and infectiousness. However, the vaccines were more effective against the Alpha variant than the Delta and Omicron variants.26
Vaccination Timing and Anti-SARS-CoV-2 Monoclonal Antibodies
Vaccines can be administered at any time after receiving anti-SARS-CoV-2 monoclonal antibodies (mAbs).27
Vaccination Timing and Immunosuppressive Therapies
If possible, COVID-19 vaccines should be administered at least 2 weeks before initiating or resuming immunosuppressive therapies. The timing of the vaccination should be determined based on the patient’s current or planned immunosuppressive therapies, as well as the patient’s medical condition and predicted response to the vaccine. Guidance about the timing of COVID-19 vaccination in solid organ transplant, HCT, and cellular immunotherapy candidates can be found in Special Considerations in Solid Organ Transplant, Hematopoietic Cell Transplant, and Cellular Immunotherapy Candidates, Donors, and Recipients. The CDC guidance allows the use of additional bivalent vaccine doses in people who are immunocompromised. Each additional dose should be administered at least 2 months after the last dose.
HCT and CAR T-cell recipients who received doses of COVID-19 vaccines prior to or during treatment with an HCT or CAR T-cell therapy should be revaccinated with a primary vaccine series at least 3 months after the transplant or CAR T-cell therapy.28 The American Society of Hematology has specific guidance about the timing of COVID-19 vaccination around cancer chemotherapy,28 and the American College of Rheumatology also provides guidance for temporarily stopping immunosuppressive regimens during vaccination.29
Polyethylene Glycol Allergies
The BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) mRNA bivalent vaccines contain polyethylene glycol (PEG), whereas the NVX-CoV2373 (Novavax) vaccine contains polysorbate 80. PEG and polysorbate are used in many products, including in agents used for cancer chemotherapy (e.g., PEG-asparaginase). PEG and polysorbate are structurally related, and cross-reactive hypersensitivity between these compounds might occur. The detection of PEG antibodies has not been shown to correlate with adverse reactions.30 Therefore, testing for anti-PEG antibodies should not be used as a screening tool to assess the risk of allergic reactions31 and should not replace an assessment by a specialist in those rare individuals with a history of anaphylaxis.32 The CDC has issued guidance on triaging people with a history of allergies or allergic reactions to the components of COVID-19 vaccines.
Tixagevimab plus cilgavimab (Evusheld) is the only anti-SARS-CoV-2 mAb regimen that was shown to be effective for pre-exposure prophylaxis (PrEP) of COVID-19, and it was the only mAb regimen that was authorized by the Food and Drug Administration (FDA) for this use. However, nearly all currently circulating Omicron subvariants in the United States are not susceptible to this combination. Therefore, tixagevimab plus cilgavimab is not currently authorized by the FDA for use as PrEP of COVID-19, and there are currently no other options for PrEP. The Panel recommends against the use of anti-SARS-CoV-2 mAbs such as tixagevimab plus cilgavimab (Evusheld) for PrEP of COVID-19 (AIII).
Serologic Testing to Guide Vaccination Strategies
There is insufficient evidence for the Panel to recommend either for or against the use of SARS-CoV-2 serologic testing to assess for immunity or to guide clinical decisions about using COVID-19 vaccines. More than 80 SARS-CoV-2 serologic tests, including quantitative, semiquantitative, neutralizing antibody, and point-of-care tests, have been issued Emergency Use Authorizations (EUAs) by the FDA to aid in detecting antibodies to SARS-CoV-2.33 However, these tests are not currently authorized for routine use in making individual medical decisions, and their ability to assess a person’s level of immunity or protection from SARS-CoV-2 infection has not been evaluated.34 Most of these tests have not been calibrated to a reference standard, limiting the ability to compare and reproduce results from different tests.
Management of Patients With COVID-19 Who Are Immunocompromised
Adjusting Chronic Immunosuppressive Therapies
The Panel recommends that decisions regarding stopping or adjusting the doses of immunosuppressive drugs in patients with COVID-19 be made in consultation with the appropriate specialists (BIII). When selecting treatments for COVID-19, clinicians should consider factors such as the underlying disease; the specific immunosuppressants being used; the potential for drug-drug interactions, overlapping toxicities, and secondary infections; and the severity of COVID-19.
Early in the clinical course of COVID-19, the disease is primarily driven by the replication of SARS-CoV-2. Immunosuppressive medications can reduce the host immune responses that suppress viral replication, increasing the risk of prolonged viral shedding and infection.35,36 Clinicians should consider adjusting the doses of immunosuppressive medications or substituting certain immunosuppressive medications, if possible, to improve the patient’s immune response to infection. When making decisions about stopping or reducing the dose of immunosuppressive drugs, clinicians should balance the potential benefit of enhancing the patient’s immune response to COVID-19 with the risk of exacerbating the underlying condition. They should also consider the role of immunomodulation in the treatment of COVID-19.
Clinicians should be aware that many immunosuppressive drugs, particularly biologic agents, have long half-lives or prolonged periods of biologic activity. Patients may remain immunosuppressed long after the drugs are stopped. Care should be taken to not stop glucocorticoids abruptly, since this may result in adrenal insufficiency. For medications other than glucocorticoids, decisions about dose adjustments should be made on a case-by-case basis. For example, for some autoimmune diseases, temporary cessation of immunosuppression is often possible, and restarting medications 7 to 14 days after symptom resolution may be appropriate.29,37
For solid organ transplant recipients, adjustments to immunosuppressive regimens should be individualized based on disease severity, the risk of graft rejection, the specific immunosuppressants being used, the type of transplant, the time since transplantation, the concentration of immunosuppressants, and the potential for drug-drug interactions.38 See Special Considerations in Solid Organ Transplant, Hematopoietic Cell Transplant, and Cellular Immunotherapy Candidates, Donors, and Recipients for more information.
Therapeutic Management of Nonhospitalized Patients With COVID-19
For nonhospitalized patients with mild to moderate COVID-19 who are immunocompromised, the Panel recommends prompt treatment with antiviral drugs at the doses and durations recommended for the general population (AIII). See Therapeutic Management of Nonhospitalized Adults With COVID-19 to review the Panel’s recommendations. Some special considerations for using these therapies in people who are immunocompromised are outlined below.
Ritonavir-Boosted Nirmatrelvir (Paxlovid)
In the EPIC-HR trial, the use of ritonavir-boosted nirmatrelvir reduced the risk of hospitalization or death when compared with placebo in nonhospitalized, unvaccinated adults who had laboratory-confirmed SARS-CoV-2 infection and a high risk of progressing to severe COVID-19.39 Because the trial did not enroll many participants who were immunocompromised, the efficacy of ritonavir-boosted nirmatrelvir was not established for this population. In subsequent retrospective studies, some potential benefits of using ritonavir-boosted nirmatrelvir in people with various immunocompromising conditions have been observed.40,41
Because ritonavir-boosted nirmatrelvir is the only highly effective oral antiviral therapy for COVID-19, it should be considered for patients who are immunocompromised if there are no potential drug-drug interactions or if the potential interactions can be safely managed. Clinicians should be aware of drug-drug interactions that may be life- or organ-threatening (see Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir [Paxlovid] and Concomitant Medications).42 Notably, calcineurin inhibitors (e.g., tacrolimus, cyclosporine A) and mammalian target of rapamycin (mTOR) drugs (e.g., sirolimus, everolimus) have important drug-drug interactions with ritonavir. For this reason, the American Society of Transplantation recommends preferentially using other therapies, such as remdesivir, over ritonavir-boosted nirmatrelvir in people who are taking calcineurin inhibitors or mTOR inhibitors.38 Ritonavir can inhibit the metabolism of many cancer-directed therapies and should only be given after consulting with specialty pharmacists and other appropriate specialists.
Case reports have described reoccurring COVID-19 symptoms and positive SARS-CoV-2 test results in some patients who have completed treatment with ritonavir-boosted nirmatrelvir.43 A randomized trial is currently evaluating the effectiveness of longer courses or a second course of ritonavir-boosted nirmatrelvir (ClinicalTrials.gov Identifier NCT05438602). People with COVID-19 who are immunocompromised should not delay or avoid taking ritonavir-boosted nirmatrelvir due to concerns about the rebound of symptoms after treatment completion (see Ritonavir-Boosted Nirmatrelvir [Paxlovid]).
Remdesivir was studied in nonhospitalized patients with mild to moderate COVID-19 who were at high risk of progressing to severe disease, and it was shown to be highly effective in reducing the risk of hospitalization and death.44 However, this trial only included a small number of participants who were immunocompromised. Because remdesivir treatment for nonhospitalized patients requires an intravenous infusion for 3 consecutive days, there may be logistical constraints to administering this drug in many settings. It can be considered for patients who are immunocompromised if other options, such as ritonavir-boosted nirmatrelvir, are not appropriate or available.
In the MOVe-OUT trial, molnupiravir reduced the rate of hospitalization or death when compared with placebo in nonhospitalized patients with COVID-19.45 However, this trial only enrolled a small number of participants who were immunocompromised. The PANORAMIC trial enrolled a larger population of people who were immunocompromised, but this population was heterogeneous and the results of the study were inconclusive.46 Although the different treatment options have not been directly compared in clinical trials, the available evidence suggests that molnupiravir has a lower efficacy than the other options (see Molnupiravir). Other COVID-19 therapies should be prioritized over molnupiravir in patients who are immunocompromised.
COVID-19 Convalescent Plasma
There is insufficient evidence for the Panel to recommend either for or against the use of high-titer COVID-19 convalescent plasma (CCP) for the treatment of COVID-19 in nonhospitalized patients who are immunocompromised. The FDA issued an EUA that allows the use of high-titer CCP for the treatment of COVID-19 in nonhospitalized or hospitalized patients who have immunosuppressive disease or are receiving immunosuppressive treatment.47 However, the evidence generated from well-designed clinical trials that evaluated the use of CCP for the treatment of nonhospitalized patients is conflicting; these trials only enrolled a small number of patients who were immunocompromised.48-51
For a discussion on the potential use of high-titer CCP in patients who are immunocompromised and have prolonged viral replication, see the Therapeutic Management of Patients With COVID-19 Symptoms and Prolonged SARS-CoV-2 Replication section below.
Some individuals who are immunocompromised and have hypogammaglobulinemia are candidates for receiving supplemental antibodies in the form of intravenous immunoglobulin (IVIG) for the prevention of a variety of infections and in the setting of acute infections, including COVID-19. IVIG can be administered as outpatient or inpatient therapy. However, outside these specific circumstances, the Panel recommends against the use of IVIG for the prevention or treatment of acute COVID-19 in adults and children, except in a clinical trial (AIII). This recommendation should not preclude the use of IVIG when it is otherwise indicated for underlying conditions. See Intravenous Immunoglobulin for more information.
Therapeutic Management of Patients Who Are Hospitalized for COVID-19
For most hospitalized patients with severe or critical COVID-19 who are immunocompromised, the Panel recommends using antiviral drugs and immunomodulatory therapies at the doses and durations recommended for the general population (AIII). See Therapeutic Management of Hospitalized Adults With COVID-19 for more information. The optimal management strategies and treatments for COVID-19 in hospitalized patients who are immunocompromised are unknown, since these individuals were either excluded from or poorly represented in major clinical trials. Nevertheless, clinical experience and retrospective data suggest that many patients who are immunocompromised have the expected responses to standard therapies for COVID-19.
Case reports suggest that remdesivir can suppress, but does not always eliminate, viral replication in this population.52,53 In a large retrospective study of patients who were immunocompromised, patients who received remdesivir had a lower risk of mortality than patients who did not receive remdesivir.54 The optimal duration of treatment with remdesivir in patients who are immunocompromised is unknown. Some clinicians may choose to extend the course of antiviral therapy past 5 to 10 days in patients who are immunocompromised, given the risk of prolonged viral replication. Given the increased likelihood of prolonged viral replication in patients receiving immunomodulatory therapy, clinicians may consider adding remdesivir to patients who are immunocompromised and have severe respiratory impairment due to COVID-19 (i.e., those who require high-flow nasal cannula [HFNC] oxygen, noninvasive ventilation [NIV], or mechanical ventilation), even though remdesivir has not been shown to confer a benefit in these patients in clinical trials.
The RECOVERY trial reported a survival benefit for dexamethasone in inpatients with COVID-19 who were receiving oxygen, HFNC oxygen, NIV, or mechanical ventilation; however, specific data regarding the subgroup of patients who were immunocompromised are not available.55 Unless otherwise indicated, corticosteroids should not be used for the treatment of COVID-19 in patients who are not receiving oxygen. In the RECOVERY trial, no survival benefit was observed for dexamethasone among the subset of patients with COVID-19 who did not require supplemental oxygen at enrollment. In an observational cohort study of U.S. veterans, the use of dexamethasone was associated with higher mortality in hospitalized patients with COVID-19 who did not require supplemental oxygen.55,56
Patients who are immunocompromised may experience delayed development of favorable adaptive responses and a prolonged period of viral replication, as discussed above. For patients who are immunocompromised, are receiving minimal levels of conventional oxygen, and are earlier in the course of COVID-19 (e.g., those with <10 days of symptoms), the preferred approach may be emphasizing supportive care, using antiviral therapy, and avoiding corticosteroids. This strategy may reduce the duration of viral replication and the risk of secondary infections. Dexamethasone should be added if the patient has escalating oxygen requirements.
For patients who are immunocompromised and who were on chronic corticosteroids prior to hospitalization, the optimal dose of dexamethasone for the treatment of COVID-19 is unknown. The recommended dose of dexamethasone is 6 mg, which is equivalent to 40 mg of prednisone. This is the minimum dose of a steroid that should be used. Maintenance doses of corticosteroids should be discontinued while a patient is receiving dexamethasone, and the doses should be resumed as soon as possible after the patient recovers from COVID-19 or completes the course of dexamethasone.
Interleukin-6 Inhibitors and Janus Kinase Inhibitors
Randomized trials have shown that adding interleukin (IL)-6 inhibitors and Janus kinase (JAK) inhibitors to dexamethasone improves clinical outcomes in patients with severe or critical COVID-19. These trials generally excluded patients who were immunocompromised or only included small numbers of these patients.57-59 For patients who are immunocompromised, the use of these agents may provide a clinical benefit similar to the benefit seen in the general population. However, it is not clear whether augmenting immunomodulation in this population increases the risk of serious bacterial, invasive fungal, or parasitic infections.
For most patients who are immunocompromised, adding IL-6 or JAK inhibitors to dexamethasone is reasonable for those who are hypoxemic and experiencing clinical progression. This follows the Panel’s treatment recommendations for the general population (see Therapeutic Management of Hospitalized Adults With COVID-19). However, clinicians should consult with specialists to ensure that the risks of using additional immunosuppressive medications, including the risks of serious infections, do not outweigh the benefits. The patient should be closely monitored for infections.
COVID-19 Convalescent Plasma
There is insufficient evidence for the Panel to recommend either for or against the use of high-titer CCP for the treatment of COVID-19 in hospitalized patients who are immunocompromised. Three key randomized trials that evaluated the use of CCP for the treatment of COVID-19—RECOVERY, CONCOR-1, and REMAP-CAP—reported no evidence of a benefit of CCP in hospitalized patients with COVID-19. However, most of the patients enrolled in these trials were not immunocompromised.60-62 Some of the subgroup analyses generated from clinical trials that enrolled patients who were immunocompromised suggested a potential benefit of CCP in this population,62-64 but subgroup analyses need to be interpreted with caution (see Table 4c). Other clinical data from case series, retrospective case-control studies, and meta-analyses have been cited as support for the potential benefit of CCP in patients who are immunocompromised.65-73 However, the patient populations differed across studies, and the studies had design limitations, making the findings difficult to interpret.
The RECOVER trial was a small, randomized trial that evaluated the use of plasma from donors who were convalescent and/or vaccinated against COVID-19 as a treatment for COVID-19 in hospitalized people with cancer, people with immunosuppression, people with lymphopenia and D-dimer levels >1 µg/mL, and people aged >75 years. Only the subgroup of patients with cancer who received plasma treatment experienced a shorter median time to improvement and lower mortality when compared with the control arm.63
For a discussion on the potential use of high-titer CCP in patients who are immunocompromised and have prolonged viral replication, see the Therapeutic Management of Patients With COVID-19 Symptoms and Prolonged SARS-CoV-2 Replication section below.
Therapeutic Management of Patients Who Are Hospitalized for Reasons Other Than COVID-19
People who are immunocompromised and have COVID-19 but were hospitalized for conditions other than COVID-19 should receive the same treatments as nonhospitalized patients (AIII). See Therapeutic Management of Nonhospitalized Adults With COVID-19 for more information.
Therapeutic Management of Patients With COVID-19 Symptoms and Prolonged SARS-CoV-2 Replication
For patients who are immunocompromised and have prolonged COVID-19 symptoms and evidence of ongoing viral replication (e.g., those with a low cycle threshold value, as measured by a reverse transcription polymerase chain reaction result or with a positive rapid antigen test result) despite receiving a course of antiviral therapy, the optimal management is unknown. Case reports and case series have documented the treatment of these patients with additional antiviral treatments, prolonged courses of antiviral treatments, high-titer CCP, or combination therapy.74-78 The data for these approaches are not definitive, but some Panel members would use 1 or more of the following treatment options:
- Longer and/or additional courses of ritonavir-boosted nirmatrelvir
- Longer and/or additional courses of remdesivir
- High-titer CCP from a vaccinated donor who recently recovered from COVID-19 likely caused by a SARS-CoV-2 variant similar to the variant causing the patient’s illness
Clinicians should be aware that the drug-drug interaction potential of ritonavir may change based on the duration of treatment. Even though cytochrome P450 (CYP) 3A4 inhibition by ritonavir is the primary concern when a 5-day course of ritonavir is used, clinicians should take into account that induction properties may become clinically relevant when ritonavir is used for 10 days or longer.79
After discontinuing longer courses of ritonavir-boosted nirmatrelvir, drug-drug interactions due to CYP3A4 inhibition largely resolve within 2 to 3 days.80 Drug-drug interactions that are caused by induction (e.g., CYP2C9, CYP2C19, uridine diphosphate-glucuronyltransferase) resolve gradually and variably.
Clinicians should consult experts (e.g., pharmacists and physicians with HIV expertise) for guidance on drug-drug interactions when using extended courses of ritonavir-boosted nirmatrelvir. For more information, see Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Concomitant Medications. The Liverpool COVID-19 Drug Interactions website provides guidance on managing drug-drug interactions in patients who are receiving for extended courses (i.e., ≥10 days) of ritonavir-boosted nirmatrelvir.
Considerations in Pregnant and Lactating People
Multiple studies have found that pregnant individuals have an increased risk of severe COVID-19 compared to age-matched controls, with increased rates of ICU admission, mechanical ventilation, extracorporeal membrane oxygenation, and death.81-83 Although hormonally mediated immunomodulation occurs during pregnancy, pregnancy is not a state of systemic immunosuppression. Changes in the immune response to certain infectious pathogens during pregnancy may increase the severity of respiratory illness in pregnant individuals. Physiologic changes, such as reduced pulmonary residual capacity, may also contribute to respiratory disease severity.84-87 Pregnant people who have underlying immunocompromising conditions or are receiving immunosuppressive medications likely have an even higher risk of severe disease. This patient group should be prioritized for the prevention and treatment of COVID-19.
The Panel recommends COVID-19 vaccination as soon as possible for everyone who is eligible according to the CDC’s Advisory Committee on Immunization Practices (ACIP), including pregnant individuals (AI). COVID-19 vaccination is strongly recommended for pregnant individuals due to their increased risk for severe disease.88,89 Vaccination is especially important for pregnant people with concomitant risk factors such as underlying immunocompromising conditions (including those who are receiving immunosuppressive medications), as the risk for severe disease is likely additive.82
Although pregnant patients have been excluded from the majority of the clinical trials that evaluated the use of COVID-19 therapeutics, pregnant patients with COVID-19 can be treated the same as nonpregnant patients, with a few exceptions. Pregnant patients who are immunocompromised or who have other risk factors likely have an even higher risk of severe COVID-19 and should be prioritized for treatment. Providers should refer to Pregnancy, Lactation, and COVID-19 Therapeutics for the Panel’s guidance on treating COVID-19 in pregnant and lactating patients. Pregnant people who are immunocompromised comprise a heterogeneous group of patients, ranging from those who are mildly immunocompromised to those who are severely immunocompromised. Evaluating and managing pregnant patients require collaboration from a multidisciplinary team. This team should include a transplant or specialty provider, an obstetrician or maternal-fetal medicine specialist, a pediatrics or neonatology specialist, and a pharmacist.
Considerations in Children
Although the overall risk of critical illness and death related to COVID-19 is lower in children than adults, severe disease does occur, particularly in children with risk factors such as moderate to severe immunocompromising conditions. See Special Considerations in Children for a discussion of the risk factors for severe COVID-19 in children, and see Therapeutic Management of Nonhospitalized Children With COVID-19 for the Panel’s framework for assessing a child’s risk of progression to severe COVID-19 based on vaccination status, comorbidities, and age.
The Panel recommends COVID-19 vaccination as soon as possible for everyone who is eligible according to the CDC’s ACIP, including children (AI).
The majority of children with mild to moderate COVID-19 will not progress to more severe illness; therefore, the Panel recommends managing these patients with supportive care alone (AIII). Few children, if any, have been enrolled in clinical trials of treatments for COVID-19. Among the children who were enrolled, very few were immunocompromised. Therefore, clinicians should be cautious when applying recommendations based on adult data to children. Clinicians need to consider the potential risks and benefits of therapy, the severity of the patient’s disease, and underlying risk factors. See Therapeutic Management of Hospitalized Children With COVID-19 and Therapeutic Management of Nonhospitalized Children With COVID-19 for the Panel’s treatment recommendations in these scenarios.
- Wallace BI, Kenney B, Malani PN, et al. Prevalence of immunosuppressive drug use among commercially insured US adults, 2018–2019. JAMA Netw Open. 2021;4(5):e214920. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34014329.
- Vijenthira A, Gong IY, Fox TA, et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood. 2020;136(25):2881-2892. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33113551.
- Conway R, Grimshaw AA, Konig MF, et al. SARS-CoV-2 infection and COVID-19 outcomes in rheumatic diseases: a systematic literature review and meta-analysis. Arthritis Rheumatol. 2022;74(5):766-775. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34807517.
- Song Q, Bates B, Shao YR, et al. Risk and outcome of breakthrough COVID-19 infections in vaccinated patients with cancer: real-world evidence from the National COVID Cohort Collaborative. J Clin Oncol. 2022;40(13):1414-1427. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35286152.
- Ao G, Wang Y, Qi X, et al. The association between severe or death COVID-19 and solid organ transplantation: a systematic review and meta-analysis. Transplant Rev (Orlando). 2021;35(3):100628. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34087553.
- Wang Y, Feng R, Xu J, et al. An updated meta-analysis on the association between HIV infection and COVID-19 mortality. AIDS. 2021;35(11):1875-1878. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34397487.
- MacKenna B, Kennedy NA, Mehrkar A, et al. Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform. Lancet Rheumatol. 2022;4(7):e490-e506. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35698725.
- Bastard P, Rosen LB, Zhang Q, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4585. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32972996.
- Strangfeld A, Schäfer M, Gianfrancesco MA, et al. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis. 2021;80(7):930-942. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33504483.
- Sharifian-Dorche M, Sahraian MA, Fadda G, et al. COVID-19 and disease-modifying therapies in patients with demyelinating diseases of the central nervous system: a systematic review. Mult Scler Relat Disord. 2021;50:102800. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33578206.
- Qutub M, Aldabbagh Y, Mehdawi F, et al. Duration of viable SARS-CoV-2 shedding from respiratory tract in different human hosts and its impact on isolation discontinuation polices revision: a narrative review. Clin Infect Pract. 2022;13:100140. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35190799.
- Kemp SA, Collier DA, Datir RP, et al. SARS-CoV-2 evolution during treatment of chronic infection. Nature. 2021;592(7853):277-282. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33545711.
- Corey L, Beyrer C, Cohen MS, et al. SARS-CoV-2 variants in patients with immunosuppression. N Engl J Med. 2021;385(6):562-566. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34347959.
- Leung WF, Chorlton S, Tyson J, et al. COVID-19 in an immunocompromised host: persistent shedding of viable SARS-CoV-2 and emergence of multiple mutations: a case report. Int J Infect Dis. 2022;114:178-182. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34757008.
- Ku JH, Sy LS, Qian L, et al. Vaccine effectiveness of the mRNA-1273 3-dose primary series against COVID-19 in an immunocompromised population: a prospective observational cohort study. Vaccine. 2023;41(24):3636-3646. Available at: https://www.ncbi.nlm.nih.gov/pubmed/37173268.
- Centers for Disease Control and Prevention. Interim clinical considerations for use of COVID-19 vaccines currently approved or authorized in the United States. 2023. Available at: https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html. Accessed February 3, 2023.
- Food and Drug Administration. Coronavirus (COVID-19) update: FDA authorizes changes to simplify use of bivalent mRNA COVID-19 vaccines. 2023. Available at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-changes-simplify-use-bivalent-mrna-covid-19-vaccines. Accessed July 6, 2023.
- Yechezkel M, Samuel Faust J, Netzer D, et al. COVID-19 vaccine booster cadence by immunocompromised status. medRxiv. 2023;Preprint. Available at: https://www.medrxiv.org/content/10.1101/2023.04.18.23288615v1.
- Link-Gelles R, Weber ZA, Reese SE, et al. Estimates of bivalent mRNA vaccine durability in preventing COVID-19-associated hospitalization and critical illness among adults with and without immunocompromising conditions—VISION Network, September 2022–April 2023. MMWR Morb Mortal Wkly Rep. 2023;72(21):579-588. Available at: https://www.ncbi.nlm.nih.gov/pubmed/37227984.
- Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-416. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33378609.
- Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020;383(27):2603-2615. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33301246.
- Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325(21):2204-2206. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33950155.
- Barrière J, Chamorey E, Adjtoutah Z, et al. Impaired immunogenicity of BNT162b2 anti-SARS-CoV-2 vaccine in patients treated for solid tumors. Ann Oncol. 2021;32(8):1053-1055. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33932508.
- Pearce FA, Lim SH, Bythell M, et al. Antibody prevalence after 3 or more COVID-19 vaccine doses in 23,000 immunosuppressed individuals: a cross-sectional study from MELODY. medRxiv. 2023;Preprint. Available at: https://www.medrxiv.org/content/10.1101/2023.02.09.23285649v1.
- Salo J, Hägg M, Kortelainen M, et al. The indirect effect of mRNA-based COVID-19 vaccination on healthcare workers’ unvaccinated household members. Nat Commun. 2022;13(1):1162. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35246536.
- Madewell ZJ, Yang Y, Longini IM Jr, Halloran ME, Dean NE. Household secondary attack rates of SARS-CoV-2 by variant and vaccination status: an updated systematic review and meta-analysis. JAMA Netw Open. 2022;5(4):e229317. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35482308.
- Centers for Disease Control and Prevention. FAQs for the interim clinical considerations for COVID-19 vaccination. 2023. Available at: https://www.cdc.gov/vaccines/covid-19/clinical-considerations/faq.html. Accessed April 28, 2023.
- American Society of Hematology. ASH-ASTCT COVID-19 vaccination for HCT and CAR T cell recipients: frequently asked questions. 2022. Available at: https://www.hematology.org/covid-19/ash-astct-covid-19-vaccination-for-hct-and-car-t-cell-recipients. Accessed July 19, 2023.
- Curtis JR, Johnson SR, Anthony DD, et al. American College of Rheumatology guidance for COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases: version 5. Arthritis Rheumatol. 2023;75(1):E1-E16. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36345691.
- Carreño JM, Singh G, Tcheou J, et al. mRNA-1273 but not BNT162b2 induces antibodies against polyethylene glycol (PEG) contained in mRNA-based vaccine formulations. Vaccine. 2022;40(42):6114-6124. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36115801.
- Bavli Y, Chen BM, Gross G, et al. Anti-PEG antibodies before and after a first dose of Comirnaty (mRNA-LNP-based SARS-CoV-2 vaccine). J Control Release. 2023;354:316-322. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36549393.
- Brockow K, Mathes S, Fischer J, et al. Experience with polyethylene glycol allergy-guided risk management for COVID-19 vaccine anaphylaxis. Allergy. 2022;77(7):2200-2210. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34806775.
- Food and Drug Administration. EUA authorized serology test performance. 2022. Available at: https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-test-performance. Accessed July 19, 2023.
- Food and Drug Administration. Antibody (serology) testing for COVID-19: information for patients and consumers. 2023. Available at: https://www.fda.gov/medical-devices/coronavirus-covid-19-and-medical-devices/antibody-serology-testing-covid-19-information-patients-and-consumers. Accessed July 19, 2023.
- Aydillo T, Gonzalez-Reiche AS, Aslam S, et al. Shedding of viable SARS-CoV-2 after immunosuppressive therapy for cancer. N Engl J Med. 2020;383(26):2586-2588. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33259154.
- Tarhini H, Recoing A, Bridier-Nahmias A, et al. Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectiousness among three immunocompromised patients: from prolonged viral shedding to SARS-CoV-2 superinfection. J Infect Dis. 2021;223(9):1522-1527. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33556961.
- Rubin DT, Feuerstein JD, Wang AY, Cohen RD. AGA clinical practice update on management of inflammatory bowel disease during the COVID-19 pandemic: expert commentary. Gastroenterology. 2020;159(1):350-357. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32283100.
- American Society of Transplantation. COVID-19: FAQs for organ transplantation. 2023. Available at: https://www.myast.org/sites/default/files/COVID%20FAQ%20for%20Tx%20professionals%202-2023%20FINAL.pdf.
- Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with COVID-19. N Engl J Med. 2022;386(15):1397-1408. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35172054.
- Najjar-Debbiny R, Gronich N, Weber G, et al. Effectiveness of Paxlovid in reducing severe coronavirus disease 2019 and mortality in high-risk patients. Clin Infect Dis. 2023;76(3):e342-e349. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35653428.
- Qian G, Wang X, Patel NJ, et al. Outcomes with and without outpatient SARS-CoV-2 treatment for patients with COVID-19 and systemic autoimmune rheumatic diseases: a retrospective cohort study. Lancet Rheumatol. 2022;5(3):e139-e150. Available at: https://pubmed.ncbi.nlm.nih.gov/36844970/.
- University Health Network. Management of nirmatrelvir/ritonavir (Paxlovid) drug-drug interactions in oncology. 2022. Available at: https://www.antimicrobialstewardship.com/paxlovid-ddi-oncology.
- Charness ME, Gupta K, Stack G, et al. Rebound of SARS-CoV-2 infection after nirmatrelvir-ritonavir treatment. N Engl J Med. 2022;387(11):1045-1047. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36069968.
- Gottlieb RL, Vaca CE, Paredes R, et al. Early remdesivir to prevent progression to severe COVID-19 in outpatients. N Engl J Med. 2022;386(4):305-315. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34937145.
- Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients. N Engl J Med. 2022;386(6):509-520. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34914868.
- Butler CC, Hobbs FDR, Gbinigie OA, et al. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet. 2023;401(10373):281-293. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36566761.
- Food and Drug Administration. Fact sheet for health care providers: Emergency Use Authorization (EUA) of COVID-19 convalescent plasma for treatment of coronavirus disease 2019 (COVID-19). 2021. Available at: https://www.fda.gov/media/141478/download.
- Libster R, Pérez Marc G, Wappner D, et al. Early high-titer plasma therapy to prevent severe COVID-19 in older adults. N Engl J Med. 2021;384(7):610-618. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33406353.
- Korley FK, Durkalski-Mauldin V, Yeatts SD, et al. Early convalescent plasma for high-risk outpatients with COVID-19. N Engl J Med. 2021;385(21):1951-1960. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34407339.
- Alemany A, Millat-Martinez P, Corbacho-Monné M, et al. High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial. Lancet Respir Med. 2022;10(3):278-288. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35150610.
- Sullivan DJ, Gebo KA, Shoham S, et al. Early outpatient treatment for COVID-19 with convalescent plasma. N Engl J Med. 2022;386(18):1700-1711. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35353960.
- Helleberg M, Niemann CU, Moestrup KS, et al. Persistent COVID-19 in an immunocompromised patient temporarily responsive to two courses of remdesivir therapy. J Infect Dis. 2020;222(7):1103-1107. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32702095.
- Gandhi S, Klein J, Robertson AJ, et al. De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report. Nat Commun. 2022;13(1):1547. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35301314.
- Mozaffari E, Chandak A, Gottlieb RL, et al. Remdesivir reduces mortality in immunocompromised patients hospitalized for COVID-19. Presented at Conference on Retroviruses and Opportunistic Infections; February 19-22, 2023; Seattle, Washington. Available at: https://www.croiconference.org/wp-content/uploads/sites/2/posters/2023/RDV_Immunocompromised_CER_CROI_poster_Feb15_for_upload-133209726333558557.pdf.
- RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384(8):693-704. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32678530.
- Crothers K, DeFaccio R, Tate J, et al. Dexamethasone in hospitalised COVID-19 patients not on intensive respiratory support. Eur Respir J. 2022;60(1):2102532. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34824060.
- Marconi VC, Ramanan AV, de Bono S, et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled Phase 3 trial. Lancet Respir Med. 2021;9(12):1407-1418. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34480861.
- Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384(9):795-807. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33306283.
- RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637-1645. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33933206.
- RECOVERY Collaborative Group. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet. 2021;397(10289):2049-2059. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34000257.
- Bégin P, Callum J, Jamula E, et al. Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial. Nat Med. 2021;27(11):2012-2024. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34504336.
- Writing Committee for the REMAP-CAP Investigators. Effect of convalescent plasma on organ support-free days in critically ill patients with COVID-19: a randomized clinical trial. JAMA. 2021;326(17):1690-1702. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34606578.
- Denkinger CM, Janssen M, Schäkel U, et al. Anti-SARS-CoV-2 antibody-containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19: a randomized clinical trial. Nat Cancer. 2023;4(1):96-107. Available at: https://pubmed.ncbi.nlm.nih.gov/36581734.
- Lacombe K, Hueso T, Porcher R, et al. COVID-19 convalescent plasma to treat hospitalised COVID-19 patients with or without underlying immunodeficiency. medRxiv. 2022;Preprint. Available at: https://www.medrxiv.org/content/10.1101/2022.08.09.22278329v2.
- Thompson MA, Henderson JP, Shah PK, et al. Association of convalescent plasma therapy with survival in patients with hematologic cancers and COVID-19. JAMA Oncol. 2021;7(8):1167-1175. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34137799.
- Lanza F, Monaco F, Ciceri F, et al. Lack of efficacy of convalescent plasma in COVID-19 patients with concomitant hematological malignancies: an Italian retrospective study. Hematol Oncol. 2022;40(5):857-863. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35932208.
- Lang-Meli J, Fuchs J, Mathé P, et al. Case series: convalescent plasma therapy for patients with COVID-19 and primary antibody deficiency. J Clin Immunol. 2022;42(2):253-265. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34893946.
- Rodionov RN, Biener A, Spieth P, et al. Potential benefit of convalescent plasma transfusions in immunocompromised patients with COVID-19. Lancet Microbe. 2021;2(4):e138. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33817676.
- Franchini M, Focosi D, Percivalle E, et al. Variant of concern-matched COVID-19 convalescent plasma usage in seronegative hospitalized patients. Viruses. 2022;14(7):1443. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35891421.
- Ljungquist O, Lundgren M, Iliachenko E, et al. Convalescent plasma treatment in severely immunosuppressed patients hospitalized with COVID-19: an observational study of 28 cases. Infect Dis (Lond). 2022;54(4):283-291. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34878955.
- Ripoll JG, Gorman EK, Juskewitch JE, et al. Vaccine-boosted convalescent plasma therapy for patients with immunosuppression and COVID-19. Blood Adv. 2022;6(23):5951-5955. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36156121.
- Senefeld JW, Klassen SA, Ford SK, et al. Use of convalescent plasma in COVID-19 patients with immunosuppression. Transfusion. 2021;61(8):2503-2511. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34036587.
- Beraud M, Goodhue Meyer E, Lozano M, et al. Lessons learned from the use of convalescent plasma for the treatment of COVID-19 and specific considerations for immunocompromised patients. Transfus Apher Sci. 2022;61(3):103355. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35063360.
- Huygens S, Gharbharan A, Serroukh Y, et al. High-titer convalescent plasma plus nirmatrelvir/ritonavir treatment for non-resolving COVID-19 in six immunocompromised patients. J Antimicrob Chemother. 2023;78(7):1644-1648. Available at: https://www.ncbi.nlm.nih.gov/pubmed/37248664.
- Brosh-Nissimov T, Ma’aravi N, Leshin-Carmel D, et al. Combination treatment of persistent COVID-19 in immunocompromised patients with remdesivir, nirmatrelvir/ritonavir and tixagevimab/cilgavimab. medRxiv. 2023;Preprint. Available at: https://www.medrxiv.org/content/10.1101/2023.04.07.23288144v1.
- Mikulska M, Sepulcri C, Dentone C, et al. Triple combination therapy with two antivirals and monoclonal antibodies for persistent or relapsed SARS-CoV-2 infection in immunocompromised patients. Clin Infect Dis. 2023;Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36976301.
- Graziani L, Gori L, Manciulli T, et al. Successful use of nirmatrelvir/ritonavir in immunocompromised patients with persistent and/or relapsing COVID-19. J Antimicrob Chemother. 2023;78(2):555-558. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36544352.
- Trottier CA, Wong B, Kohli R, et al. Dual antiviral therapy for persistent coronavirus disease 2019 and associated organizing pneumonia in an immunocompromised host. Clin Infect Dis. 2023;76(5):923-925. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36281907.
- Foisy MM, Yakiwchuk EM, Hughes CA. Induction effects on ritonavir: implications for drug interactions. Ann Pharmacother. 2008;42(7):1048-1059. Available at: https://pubmed.ncbi.nlm.nih.gov/18577765.
- Stader F, Khoo S, Stoeckle M, et al. Stopping lopinavir/ritonavir in COVID-19 patients: duration of the drug interacting effect. J Antimicrob Chemother. 2020;75(10):3084-3086. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32556272.
- Zambrano LD, Ellington S, Strid P, et al. Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22–October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(44):1641-1647. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33151921.
- Ellington S, Strid P, Tong VT, et al. Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22–June 7, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(25):769-775. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32584795.
- Allotey J, Stallings E, Bonet M, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020;370:m3320. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32873575.
- Denney JM, Nelson EL, Wadhwa PD, et al. Longitudinal modulation of immune system cytokine profile during pregnancy. Cytokine. 2011;53(2):170-7. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21123081.
- Kourtis AP, Read JS, Jamieson DJ. Pregnancy and infection. N Engl J Med. 2014;370(23):2211-8. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24897084.
- Mosby LG, Rasmussen SA, Jamieson DJ. 2009 pandemic influenza A (H1N1) in pregnancy: a systematic review of the literature. Am J Obstet Gynecol. 2011;205(1):10-8. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21345415.
- Siston AM, Rasmussen SA, Honein MA, et al. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA. 2010;303(15):1517-25. Available at: https://www.ncbi.nlm.nih.gov/pubmed/20407061.
- Centers for Disease Control and Prevention. COVID-19 vaccines while pregnant or breastfeeding. 2022. Available at: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html. Accessed July 19, 2023.
- American College of Obstetricians and Gynecologists. COVID-19 vaccination considerations for obstetric-gynecologic care. 2023. Available at: https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2020/12/covid-19-vaccination-considerations-for-obstetric-gynecologic-care. Accessed July 19, 2023.