Guidelines for the Prevention and Treatment of Opportunistic Infections in Children With and Exposed to HIV

Epidemiology

COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus (type) 2 (SARS-CoV-2) virus, which was initially identified in December 2019 and quickly spread around the globe, causing a pandemic. The virus is spread through respiratory droplets and small particles that are inhaled during close person-to-person contact or transmitted through touching mucous membranes with hands that have been contaminated by the virus.¹ The mean incubation period for SARS-CoV-2 is 3 to 5 days, with more recent variants associated with shorter incubation periods and nearly all infections occurring within 14 days of exposure.² Viral shedding begins prior to the onset of symptoms, peaks around the time of symptom onset, and gradually declines over the next 7 to 10 days. Transmission of infectious virus is unlikely after 10 days of illness; however, prolonged shedding for 20 days or longer has been described in persons with immunosuppression, including those with advanced or untreated HIV infection.^3-6

SARS-CoV-2 has evolved over time through mutations in its viral genome. Variants of interest or variants of concern are assigned letters of the Greek alphabet by the World Health Organization (WHO).⁷ Some new variants and some sublineages may have increased transmissibility or virulence, ability to evade the humoral immunity induced by vaccination or previous infection, or features that impact the effectiveness of diagnostics and therapeutics. Within the United States, the proportions of variants circulating in different parts of the country are reported on the Centers for Disease Control and Prevention (CDC) Data Tracker website.⁸

As of September 9, 2023, nearly 200,000 children under 18 years have required hospital admission for COVID-19, and more than 1,600 children have died.^8,9 COVID-19 has affected people in different racial and ethnic groups unequally. People within racial and ethnic minority groups are at increased risk of SARS-CoV-2 acquisition, COVID-19–related hospitalization, and death.^10-15 Importantly, these communities have also been disproportionately affected by the HIV epidemic.

Clinical Manifestations

SARS-CoV-2 infection can cause a range of clinical presentations, from asymptomatic infection to mild respiratory symptoms to severe organ dysfunction and death. Cough, congestion, fever, myalgias, and headache are the most common presenting symptoms of COVID-19 in adults and children. Pediatric patients with COVID-19 may present with symptoms of croup or bronchiolitis. Gastrointestinal manifestations of COVID-19 occur infrequently but are reported more often in younger populations.^15-17 Disorders of smell and taste (i.e., anosmia and dysgeusia) were reported with early variants of SARS-CoV-2, but are less common with more recent variants.¹⁸ A range of dermatologic findings, including various rashes (maculopapular, urticarial, petechial, and/or vesicular) and chilblains-like lesions on the digits, have also been reported with COVID-19.¹⁹

Children appear less likely to become severely ill with COVID-19 than adults.⁸ Severe COVID-19 in children can lead to pneumonia, acute respiratory distress syndrome, shock, and multiple organ dysfunction. Well-described complications include cardiac (e.g., arrhythmia, myocardial injury, heart failure), neurologic (e.g., seizures, encephalopathy), thromboembolic, hyperinflammatory syndromes, and death. Underlying conditions that are associated with higher rates of severe COVID-19 in children include asthma, obstructive sleep apnea, chronic lung disease, cardiac disease, neurologic disorders, obesity, diabetes, prematurity (in young infants), immunocompromising conditions (other than HIV), and medical complexity/dependence on medical technology (such as tube feeding or chronic respiratory support).^15,16,20-23 Severe COVID-19 (i.e., resulting in hospitalization, intensive care unit [ICU] admission, or mechanical ventilation) has been reported less commonly in children with later variants of SARS-CoV-2 compared to earlier variants.^17,21,24,25

It is unclear whether people with HIV are at increased risk of severe COVID-19. Observational cohort studies have shown conflicting results, with some reporting higher rates of hospitalization, ICU admission, mechanical ventilation support, and/or mortality among adults with HIV and others showing no increased risk associated with HIV infection.^26-42 Several studies identified an increased risk of severe COVID-19 among adults with advanced or untreated HIV infection compared to those on antiretroviral treatment (ART) with no evidence of immunosuppression.^34-38,41-43 Few publications have described the outcomes of children or adolescents with HIV who acquire SARS-CoV-2, but those available report mild COVID-19 symptoms and/or no increased risk of severe COVID-19 among children or adolescents with HIV.^44-48

Following infection with SARS-CoV-2, which may be asymptomatic, some children may experience a post-acute manifestation of the infection, such as multisystem inflammatory syndrome in children (MIS-C) or post-acute sequelae of SARS-CoV-2 (PASC; also known as “long COVID” or “long-hauler syndrome”). An increased rate of some autoimmune complications, such as new-onset type 1 diabetes, has also been identified in the post–COVID-19 period.^49,50

PASC is a heterogenous disorder that has been described in 4% to 66% of children after acute COVID-‍19.⁵¹ The presentation of PASC may include any of a wide-ranging constellation of symptoms that involve multiple body systems, such as:

• Neurologic (fatigue, sleep disorders, attention disorders, “brain fog,” headaches)
• Psychiatric (anxiety, depression, post-traumatic stress disorder)
• Pulmonary (cough, dyspnea)
• Cardiac (chest pain, palpitations, dizziness, exercise intolerance, autonomic dysfunction, syncope)
• Otolaryngologic (anosmia, dysgeusia)
• Musculoskeletal (arthralgias, myalgias)
• Gastrointestinal (nausea, vomiting, diarrhea, abdominal pain)

A multidisciplinary group defined PASC in children as involving one or more persistent physical symptoms, which may fluctuate and relapse, that lasts for at least 12 weeks after confirmed initial SARS-CoV-2 infection, impairs daily function, and cannot be explained by an alternative diagnosis after initial testing.⁵² Limited data suggest that adults with HIV may be at higher risk of PASC than adults without HIV, but more research is needed on the incidence of PASC in children with HIV.^53-55

MIS-C is a relatively rare postinfectious hyperinflammatory condition occurring in <1% of children 2 to 6 weeks after acute COVID-19, including following mild or asymptomatic infection.^56,57 MIS-C has been reported less commonly in children with later variants of SARS-CoV-2 compared to earlier variants. Symptoms may overlap with those of Kawasaki syndrome or toxic shock syndrome; however, MIS-‍C typically occurs in older children and adolescents (median age 8-9 years), whereas Kawasaki syndrome classically occurs in younger children <5 years of age.^58-61 CDC developed new case definitions for confirmed and probable MIS-C in January 2023, which include age <21 years, fever, clinical severity requiring hospitalization or resulting in death, C-reactive protein ≥3 mg/dL, new-onset manifestations in at least two categories (cardiac, mucocutaneous, shock, gastrointestinal, hematologic), absence of a more likely alternative diagnosis, and laboratory-confirmed SARS-CoV-2 infection (confirmed case) or exposure (probable case) in the last 60 days.⁶² More research is needed to understand MIS-C outcomes among children with HIV.

Diagnosis

The approach to diagnosing acute SARS-CoV-2 infection is identical in children with and without HIV, involving antigen tests using upper respiratory tract samples or nucleic acid amplification tests (NAAT), which are considered the most accurate. Many rapid antigen tests are available for home use. Some of the NAAT and antigen diagnostic tests for SARS-‍CoV-2 are approved for use by the U.S. Food and Drug Administration (FDA), while others are available under an Emergency Use Authorization (EUA).⁶³

SARS-CoV-2 serologic (i.e., antibody) tests can be used to determine whether prior exposure to SARS-‍CoV-2 has occurred through either vaccination or infection; however, serologic tests should not be used to make a diagnosis of acute COVID-19 because it can take 21 days or longer after symptom onset for seroconversion to occur.^64,65 SARS-CoV-2 serologic tests may have variable sensitivity and specificity, may detect different isotypes of immunoglobulins (i.e., immunoglobulin G, immunoglobulin A, and/or immunoglobulin M), and may be subject to cross-reactivity to antibodies from other coronaviruses. For these reasons, SARS-CoV-2 serologic tests should not be used to guide decisions about the use of vaccines, monoclonal antibodies, or other therapeutics to prevent or treat acute COVID-19 (AIII).

Prevention Recommendations

Preventing Exposure

Several personal preventative measures can be implemented to decrease the likelihood of SARS-‍CoV-2 spreading in community settings. Personal hygiene measures include frequent handwashing or use of an alcohol-based hand sanitizer and covering the nose and mouth while coughing and sneezing. During periods of high community transmission, the risk of SARS-CoV-2 acquisition can be decreased by avoiding crowds and close contact with people outside of the household and ensuring adequate ventilation of indoor spaces. Proper use of a well-fitted mask or face covering can also help decrease community spread of SARS-CoV-2, primarily by containing the secretions of infected persons, but also by reducing exposure of the mask wearer to the virus, with the degree of protection offered to the mask wearer dependent upon the filtration efficacy of the mask (with N95 masks having the highest filtration efficacy, followed by disposable medical masks, and finally by cloth masks).^66-68 Mask wearing is most beneficial during periods of high community transmission in settings where social distancing is difficult or impossible, as well as indoor settings with poor ventilation. People who acquire SARS-CoV-2 should isolate at home until at least 24 hours after their symptoms begin improving and fever has resolved to prevent spreading the infection to others.^69,70

In the health care setting, infection prevention interventions to reduce the spread of SARS-CoV-2 include identification and isolation of people with infection, use of personal protective equipment, proper hand hygiene, and environmental disinfection. When caring for patients with COVID-19, health care providers should use a particulate respirator (i.e., N95 mask) during all aerosol-generating procedures and potentially during all interactions with the patient.⁷¹ During periods of high SARS-CoV-2 community transmission, institutions may decide to implement the universal use of face masks for everyone in a health care setting (e.g., employees, visitors).

Preventing Disease

COVID-19 vaccination effectively prevents severe outcomes such as hospitalization and post-acute COVID-19 syndromes (e.g., MIS-C and PASC) in children.^72-86 While there is evidence that vaccine effectiveness wanes over time, protection against severe disease (ICU admission, mechanical ventilation, or death) is more durable.^87,88 Several successive formulations of COVID-19 vaccines have been developed and approved or authorized for use by the FDA in an effort to best target circulating variants. For more information on currently recommended vaccine products and schedules, see CDC’s Use of COVID-19 Vaccines in the United States. In the United States, COVID-19 vaccines have been authorized for children aged ≥6 months since June 2022.⁸⁹ Clinical trials evaluating COVID-19 vaccines in infants <6 months of age are ongoing (e.g., NCT05584202). Although no COVID-19 vaccines are yet approved for children <6 months of age, maternal immunization during pregnancy has been shown to increase antibody transfer and provide protection to infants for the first 6 months of life.^90,91

All children with HIV aged ≥6 months should receive age-appropriate COVID-19 vaccines, including updated vaccines as part of routine prevention, regardless of CD4 T lymphocyte (CD4) cell count or viral load (AI). Household members and close contacts of children with HIV aged ≥6 months should also receive COVID-19 vaccines to prevent exposure to the child (AIII). Refer to CDC’s Use of COVID-19 Vaccines in the United States for the most up-to-date information about the COVID-19 vaccines available to children by age, immunocompromised status, and the recommended dosing intervals.⁸⁹ Thus far, studies of adults and children with HIV show that COVID-19 vaccines are safe and immunogenic, but humoral responses are lower in people with advanced or untreated HIV.^48,92-102 Although vaccine responses are likely to improve after initiation of ART, vaccination against COVID-19 should not be delayed while awaiting immune reconstitution (AIII). Children with HIV may receive additional doses of COVID-19 vaccines, as indicated by CDC’s COVID-19 vaccination guidance for people who are moderately or severely immunocompromised, if they have stage 3 HIV infection (see HIV Infection Stage table in the Introduction), history of an AIDS-defining illness without immune reconstitution, clinical manifestations of symptomatic HIV, or untreated HIV infection.

There are very few contraindications or precautions associated with the COVID-19 vaccines, and these precautions are identical for children with and without HIV.⁸⁹ Common side effects that may occur after receipt of vaccines include local reactions (pain, swelling, or redness at the injection site), ipsilateral axillary lymphadenopathy, and such systemic reactions as fever, fatigue, headache, or myalgias. Anaphylaxis or syncope may occur rarely in the immediate post-vaccination period. Myocarditis and/or pericarditis has been described (see CDC’s Clinical Considerations: Myocarditis and Pericarditis after Receipt of COVID-19 Vaccines) most frequently among adolescent or young adult males, typically in the week after receiving a second dose or subsequent dose of a messenger RNA (mRNA) COVID-19 vaccine. Myocarditis or pericarditis is estimated to be a rare outcome (up to two cases per 10,000 mRNA vaccine doses), and nearly all cases are mild and result in full recovery.¹⁰³ In addition, cardiac complications are estimated to occur at a rate two- to sixfold higher among adolescent males ages 12 to 17 years after SARS-CoV-2 infection than after mRNA vaccination.¹⁰⁴

Pemivibart (Pemgarda^TM) is a recombinant human monoclonal antibody that was authorized by the FDA in March 2024 for use as pre-exposure prophylaxis against COVID-19 in adults and adolescents aged ≥12 years and who weigh ≥40 kg with moderate-to-severe immunocompromise (including those with advanced or untreated HIV infection) who are unlikely to have an adequate response to COVID-19 vaccination.^105,106 Pemivibart is administered intravenously in a health care setting with a post-infusion observation period of 2 hours due to the possibility of anaphylaxis. Doses can be repeated every 3 months if the risk of exposure to SARS-CoV-2 and moderate-to-severe immunocompromise persist. While pemivibart is the only available option for pre-exposure prophylaxis, it may be logistically challenging to administer and may not be available in all locations. For children aged ≥12 years and who weigh ≥40 kg with HIV, the Panel on Opportunistic Infections in Children with and Exposed to HIV (the Panel) recommends that pemivibart be considered for the prevention of COVID-19 in those with severe immunosuppression (stage 3 – see HIV Infection Stage table in the Introduction) regardless of COVID-19 vaccination status (BIII) and that it may be considered for those with moderate to no immunosuppression (stage 1 or 2 – see HIV Infection Stage table in the Introduction) in whom COVID-19 vaccines are contraindicated or unavailable (CIII). Monoclonal antibodies, including pemivibart, are not a substitute for vaccination in people who are eligible for COVID-19 vaccines. In individuals recently vaccinated against COVID-19, pemivibart should be administered at least 2 weeks after the most recent vaccination. Pemivibart is not authorized for post-exposure prophylaxis against COVID-19.

Treatment Recommendations

Treating Disease

The majority of pediatric SARS-CoV-2 infections are asymptomatic or mildly symptomatic, including in children and youth with HIV.⁴⁸ Isolation and supportive care with antipyretics, analgesics, hydration, and rest are the mainstays of treatment. Children who present with syndromes consistent with croup, bronchiolitis, or an asthma exacerbation and test positive for SARS-CoV-2 should receive supportive care and adjunctive treatments (including corticosteroids, if indicated) as per standard of care.

In general, the management of COVID-19 in people with HIV is similar to the management of people without HIV, with two exceptions: (1) people with advanced or untreated HIV who have COVID-19 and for whom there is concern for clinical worsening should be evaluated for opportunistic infections, and (2) people with HIV may be eligible for certain antiviral medications due to having a higher risk of progression to severe COVID-19. Of note, no clinical trials have been performed to specifically evaluate the efficacy of any currently available antiviral medications that target SARS-CoV-2 among people with HIV. In addition, very few published studies have evaluated these medications in children. Recommendations for the therapeutic management of children with COVID-19 are largely extrapolated from adult safety and efficacy data, established management of other viral infections in children, and expert opinion. The decision to use antiviral medications in children with COVID-19 should take into account the child’s risk factors for progression to severe disease, including medical comorbidities, degree of immunosuppression, and history of vaccination against COVID-19.

As the SARS-CoV-2 virus evolves over time, the efficacy of antiviral medications used to treat COVID-19 may change. Antiviral drugs currently available for use in pediatric patients <18 years of age that have activity against currently circulating SARS-CoV-2 variants include remdesivir (available to those aged ≥28 days) and ritonavir-boosted nirmatrelvir (Paxlovid) (available to those aged ≥12 years). Molnupiravir is an antiviral with an EUA for people ≥18 years of age; therefore, it will not be discussed further in this guidance.

Remdesivir (Veklury)

Remdesivir (Veklury) is approved by the FDA for the treatment of COVID-19 in adults and children aged ≥28 days and who weigh ≥3 kg who are hospitalized with COVID-19 and for those with mild to moderate COVID-19 who are not hospitalized and are at high risk of progression to severe disease. In clinical trials of non-hospitalized adolescents and adults at high risk of progression to severe COVID-19, remdesivir was associated with significant reductions in hospitalization or death.^107,108 Clinical trials that evaluated remdesivir in hospitalized adults with severe COVID-19 consistently showed benefit among a subgroup of patients who required supplemental oxygen but not mechanical ventilation.^109-112 Publications describing the use of remdesivir in children are limited to one single-arm, open-label study of 53 hospitalized children and a small number of case series; these studies reported high rates of clinical recovery and few adverse events.^113-116

Based on these data, the Panel recommends that remdesivir may be considered in the outpatient setting for treatment of laboratory-confirmed or clinically suspected mild to moderate COVID-19 in children with HIV who are aged ≥28 days and weigh ≥3 kg and are at high risk of progressing to severe COVID-19 due to advanced or untreated HIV or another high-risk condition as defined by CDC (CIII). For non-hospitalized children with HIV aged ≥12 years and at high risk of progressing to severe COVID-‍19, ritonavir-boosted nirmatrelvir is the preferred treatment, but remdesivir may be considered if ritonavir-boosted nirmatrelvir is unavailable or contraindicated (BI*). For non-hospitalized children with HIV aged <12 years and at high risk of progressing to severe COVID-19, remdesivir is currently the only treatment option but may be logistically challenging to administer and may not be available in all locations.

Among hospitalized children with HIV who are aged ≥28 days and weigh ≥3 kg with laboratory-confirmed or clinically suspected acute COVID-19, remdesivir should be considered in children who are receiving supplemental oxygen (BI*) and should be administered in children who are severely or critically ill, have a rapidly increasing oxygen requirement, and/or who are at high risk of progressing to severe COVID-19 due to advanced or untreated HIV or another high-risk condition as defined by CDC (AI*).

Remdesivir is administered intravenously once daily for 3 days to non-hospitalized patients and for 5 days or until discharge (whichever occurs first) in hospitalized patients. The duration of remdesivir for hospitalized patients who are critically ill or have immunosuppression can be extended to 10 days. Ideally, remdesivir should be started within 7 days of symptom onset, as active viral replication has often ceased after this time in the majority of previously healthy patients. However, in children with HIV with severe immunosuppression who may have prolonged viral replication and shedding, antiviral therapy could be considered even if presenting with >7 days of symptoms (CIII). Common side effects attributed to remdesivir include nausea/vomiting and elevation of serum transaminases. Although remdesivir has potential for drug–drug interactions, the potential for interactions with antiretroviral (ARV) drugs is thought to be unlikely. Providers should consult a drug interactions resource, such as the University of Liverpool COVID-19 Drug–Drug Interaction website, for further guidance.¹¹⁷

Ritonavir-Boosted Nirmatrelvir (Paxlovid)

Ritonavir-boosted nirmatrelvir (Paxlovid) is an oral protease inhibitor (PI) that has an EUA for the treatment of COVID-19 in children aged ≥12 years and who weigh ≥40 kg who are at high risk of progression to severe disease. In the EPIC-HR trial, ritonavir-boosted nirmatrelvir reduced the risk of hospitalization or death by 89% compared to placebo in non-hospitalized adults (≥18 years) with COVID-19 who were at high risk of progression to severe disease.¹¹⁸ It is unclear whether any participants had HIV. Clinical trials, such as EPIC-Peds (NCT05261139),¹¹⁹ are underway to evaluate the safety and efficacy of ritonavir-boosted nirmatrelvir in children. A case series of nine children who received ritonavir-boosted nirmatrelvir reported few adverse events and no hospitalizations after receiving treatment.¹²⁰ Ritonavir-boosted nirmatrelvir is expected to achieve similar drug exposure in adolescents aged ≥12 years and who weigh ≥40 kg as in adults, and there is extensive experience with the use of ritonavir in children.¹²¹ Based on these data, the Panel recommends that ritonavir-boosted nirmatrelvir should be considered in the outpatient setting for the treatment of laboratory-confirmed or clinically suspected mild to moderate COVID-19 in children with HIV who are aged ≥12 years and weigh ≥40 kg who are at high risk of progressing to severe COVID-19 due to advanced or untreated HIV or another high-risk condition as defined by CDC (BI*).

Ritonavir-boosted nirmatrelvir may be administered with other ARVs, including those that contain ritonavir or cobicistat, without any interruption or modification to the child’s usual antiretroviral therapy (AIII).¹²² Children taking an ARV regimen that includes ritonavir or cobicistat should be monitored for increased side effects (e.g., nausea, vomiting, diarrhea, abdominal pain, jaundice, hepatic transaminase elevations) while taking ritonavir-boosted nirmatrelvir, but the doses of ritonavir-boosted nirmatrelvir and/or the other ARVs do not need to be adjusted. Patients with untreated or poorly controlled HIV could theoretically develop PI resistance while taking ritonavir-boosted nirmatrelvir. Ritonavir-boosted nirmatrelvir has potential for drug–drug interactions due to being both a cytochrome P450 (CYP) 3A inhibitor and a CYP3A substrate. Providers should consult the FDA Paxlovid Emergency Use Authorization Fact Sheet for Healthcare Providers, the Infectious Diseases Society of America Management of Drug Interactions with Nirmatrelvir/Ritonavir (Paxlovid): Resource for Clinicians, and/or the University of Liverpool COVID-19 Drug–Drug Interaction website for guidance on drug–drug interactions. Renal and hepatic function should be evaluated prior to initiating ritonavir-boosted nirmatrelvir, and doses should be adjusted if needed.¹²¹ Ritonavir-boosted nirmatrelvir should be started within 5 days of symptom onset (BI*) and administered orally twice daily for 5 days. Patients should be advised that a small proportion of people experience “rebound” (i.e., return of symptoms, testing positive after a previous negative test, or both) 2 to 8 days after taking ritonavir-boosted nirmatrelvir.¹²³ The potential for viral rebound should not dissuade providers from offering ritonavir-boosted nirmatrelvir to patients who are at high risk of progressing to severe COVID-19 and could potentially benefit from its use (AIII). Other potential side effects of ritonavir-boosted nirmatrelvir include gastrointestinal upset (nausea, vomiting, diarrhea), altered taste, and increased blood pressure.

Other Treatment Considerations

Corticosteroids have demonstrated benefit in hospitalized adults with severe COVID-19. The RECOVERY trial reported a decrease in 28-day all-cause mortality among hospitalized adults ≥18 years of age who received 10 days of dexamethasone, with the greatest effect among adults receiving mechanical ventilation or extracorporeal membrane oxygenation (ECMO), a moderate effect among patients receiving supplemental oxygen or noninvasive positive pressure ventilation, and no effect among patients who did not require supplemental oxygen.¹²⁴ A small number of participants (<1%) had HIV. No clinical trials have evaluated the efficacy of corticosteroids in children with COVID-19. However, given the strong safety record of corticosteroids and abundant pediatric experience with corticosteroids in other settings, the possible benefits likely outweigh the potential risks in critically ill and severely ill children. Therefore, the Panel recommends that corticosteroids (such as dexamethasone) should be considered for treatment of laboratory-confirmed or clinically suspected acute COVID-19 in children with HIV who require hospitalization and are receiving supplemental oxygen (BIII) and should be administered for treatment of laboratory-confirmed or clinically suspected acute COVID-19 in children with HIV who are severely or critically ill, have a rapidly increasing oxygen requirement, and/or who are at high risk of progressing to severe COVID-19 due to advanced or untreated HIV or another high-risk condition as defined by CDC (AIII).

Dexamethasone can be administered to hospitalized children with COVID-19 orally or intravenously for ≤10 days. Dexamethasone has potential for drug–drug interactions; of particular importance to children with HIV is a potential interaction with non-nucleoside reverse transcriptase inhibitors (NNRTIs), which may result in decreased serum concentrations of either dexamethasone or the NNRTI, depending on which NNRTI is used. Providers should consult a drug interactions resource, such as the University of Liverpool COVID-19 Drug–Drug Interaction website, for further guidance. Alternative corticosteroids, such as hydrocortisone or methylprednisolone, may be considered if dexamethasone is not available or if alternative corticosteroids are being administered for another indication. Except for considering potential drug–drug interactions, recommendations for the use of corticosteroids in children hospitalized with severe COVID-19 are no different for children with and without HIV. Corticosteroids should be avoided in non-hospitalized children with COVID-19 unless they are used for an indication (e.g., croup, asthma exacerbation).

Anti-inflammatory medications—such as anakinra, baricitinib, tocilizumab, and tofacitinib—have been used in hospitalized adults with severe COVID-19. Of note, the EUAs of baricitinib and tocilizumab for hospitalized patients with COVID-19 include children as young as 2 years of age.^125,126 Several of these medications have been used in other pediatric rheumatologic or inflammatory disorders. However, there is less experience with the use of these anti-inflammatory agents than with corticosteroids in children with COVID-19. These anti-inflammatory medications can be considered on a case-by-case basis in children with HIV who are hospitalized with severe COVID-19 (i.e., requiring mechanical ventilation or ECMO, with critical illness, or with evidence of hyperinflammation) who are not improving despite treatment with antivirals and corticosteroids (CIII). The choice of anti-inflammatory agent may differ among institutions; consultation with a pediatric rheumatologist is suggested. Recommendations for the use of anti-inflammatory medications in children hospitalized with severe COVID-19 are no different for children with and without HIV.

Anticoagulation is often used in hospitalized adults with COVID-19 to prevent thromboembolic disease. In two large case series of children hospitalized with acute symptomatic COVID-19, between 1% to 2% experienced a thromboembolic complication.^127,128 No trials to define the optimal approach to anticoagulation have been conducted among hospitalized children with COVID-19. Prophylactic anticoagulation can be considered in hospitalized children with HIV with COVID-19 according to local institutional guidelines and consideration of the patient’s underlying risk factors for thromboembolic disorders (CIII). Recommendations for the use of prophylactic anticoagulation in children hospitalized with COVID-19 are no different for children with and without HIV.

Managing Treatment Failure

In children hospitalized for severe COVID-19, high-quality supportive care in a pediatric critical care unit is vital to recovery. The duration of remdesivir can be extended to 10 days in critically ill patients that have not shown substantial improvement by Day 5. Corticosteroids can also be used for up to 10 days in children who are severely or critically ill. Immune modulation (e.g., treatment with anti-inflammatory medications, such as anakinra, baricitinib, tocilizumab, and tofacitinib) has been used in children who are not improving despite treatment with antivirals and corticosteroids.

Managing Multisystem Inflammatory Syndrome in Children

The approach to treating MIS-C is identical in children with and without HIV. Supportive management is tailored to the patient’s presenting symptoms and degree of clinical severity and should include fluid resuscitation, inotropic support, and respiratory support as needed. MIS-C is typically treated with anti-inflammatory medications, although the choice of agents (e.g., corticosteroids, intravenous immune globulin, anakinra, infliximab), dose, and duration used varies between institutions. The American College of Rheumatology has developed clinical guidance documents for the management of MIS-C.

Managing Post-acute Sequelae of SARS-CoV-2

The approach to treating PASC is identical in children with and without HIV. Some symptoms (e.g., anosmia) may require only watchful waiting, whereas others (e.g., heart palpitations, psychiatric symptoms) may require diagnostic testing and/or referral to a subspecialist. Symptoms of fatigue and exercise intolerance may benefit from a gradual increase in physical activity through an exercise program, possibly with oversight from a physical or occupational therapist. In some locations, multidisciplinary clinics have been formed to manage pediatric PASC, but these are not likely to be accessible for all children. Further guidance on the management of pediatric PASC can be found in published consensus statements from the Multi-Disciplinary Post-Acute Sequelae of SARS-CoV-2 Infection Collaborative and the American Academy of Pediatrics.

Management of HIV During the COVID-19 Pandemic

During periods of elevated community transmission of SARS-CoV-2, clinicians managing HIV should make every effort to maintain routine health care visits and viral load monitoring. Health care facilities should offer virtual (telehealth) visits, if possible, for patients isolating at home or patients who wish to avoid potential exposure to COVID-19. The importance of maintaining adherence to ART should be emphasized, and clinicians should ensure that people with HIV can access an adequate supply of ART. One such strategy includes providing refills every 3 or 6 months instead of every 30 days. There is no evidence that any ARVs used for the treatment of HIV (e.g., lopinavir/‌ritonavir, boosted darunavir, or tenofovir disoproxil fumarate/emtricitabine) have efficacy against SARS-CoV-2; therefore, children with HIV should not change their ARV regimen in an effort to prevent or treat COVID-19 (AIII). When children with HIV acquire SARS-CoV-2, regardless of whether they require hospitalization or treatment for COVID-‍19, they should continue their usual ART (AIII). Clinicians should note that lymphopenia is a common laboratory finding in patients with COVID-19 (and MIS-C); therefore, in patients with HIV, the CD4 counts obtained during acute COVID-19 or MIS-C may not accurately reflect the HIV disease stage.

References

1. Meyerowitz EA, Richterman A, Gandhi RT, Sax PE. Transmission of SARS-CoV-2: a review of viral, host, and environmental factors. Ann Intern Med. 2021;174(1):69-79. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32941052.
2. Wu Y, Kang L, Guo Z, Liu J, Liu M, Liang W. Incubation period of COVID-19 caused by unique SARS-CoV-2 strains: a systematic review and meta-analysis. JAMA Netw Open. 2022;5(8):e2228008. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35994285.
3. Peters JL, Fall A, Langerman SD, et al. Prolonged severe acute respiratory syndrome coronavirus 2 delta variant shedding in a patient with AIDS: case report and review of the literature. Open Forum Infect Dis. 2022;9(9):ofac479. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36193230.
4. 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.
5. Meiring S, Tempia S, Bhiman JN, et al. Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at high viral loads among hospitalized immunocompromised persons living with human immunodeficiency virus (HIV), South Africa. Clin Infect Dis. 2022;75(1):e144-e156. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35134129.
6. Ikeda D, Fukumoto A, Uesugi Y, et al. Clinical and immunological characteristics of prolonged SARS-CoV-2 Omicron infection in hematologic disease. Blood Cancer J. 2023;13(1):133. Available at: https://www.ncbi.nlm.nih.gov/pubmed/37666820.
7. World Health Organization. Tracking SARS-CoV-2 variants. 2023. Available at: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants.
8. Centers for Disease Control and Prevention. COVID data tracker. Atlanta, GA: U.S. Department of Health and Human Services, CDC. 2023. Available at: https://covid.cdc.gov/covid-data-tracker/#variant-proportions.
9. Centers for Disease Control and Prevention. Deaths by select demographic and geographic characteristics. 2023. Available at: https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm#SexAndAge.
10. Centers for Disease Control and Prevention. Risk for COVID-19 infection, hospitalization, and death by race/ethnicity. 2021. Available at: https://stacks.cdc.gov/view/cdc/105022.
11. Kim L, Whitaker M, O’Halloran A, et al. Hospitalization rates and characteristics of children aged <18 years hospitalized with laboratory-confirmed COVID-19 - COVID-NET, 14 states, March 1–July 25, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(32):1081-1088. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32790664.
12. Magesh S, John D, Li WT, et al. Disparities in COVID-19 outcomes by race, ethnicity, and socioeconomic status: a systematic-review and meta-analysis. JAMA Netw Open. 2021;4(11):e2134147. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34762110.
13. Webb Hooper M, Napoles AM, Pérez-Stable EJ. COVID-19 and racial/ethnic disparities. JAMA. 2020;323(24):2466-2467. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32391864.
14. Vicetti Miguel CP, Dasgupta-Tsinikas S, Lamb GS, Olarte L, Santos RP. Race, ethnicity, and health disparities in U.S. children with COVID-19: a review of the evidence and recommendations for the future. J Pediatric Infect Dis Soc. 2022;11(Supplement_4):S132-S140. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36063366.
15. Graff K, Smith C, Silveira L, et al. Risk factors for severe COVID-19 in children. Pediatr Infect Dis J. 2021;40(4):e137-e145. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33538539.
16. Forrest CB, Burrows EK, Mejias A, et al. Severity of acute COVID-19 in children <18 years old March 2020 to December 2021. Pediatrics. 2022;149(4). Available at: https://www.ncbi.nlm.nih.gov/pubmed/35322270.
17. Marks KJ, Whitaker M, Agathis NT, et al. Hospitalization of infants and children aged 0–4 Years with laboratory-confirmed COVID-19 - COVID-NET, 14 states, March 2020–February 2022. MMWR Morb Mortal Wkly Rep. 2022;71(11):429-436. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35298458.
18. Coelho DH, Reiter ER, French E, Costanzo RM. Decreasing incidence of chemosensory changes by COVID-19 variant. Otolaryngol Head Neck Surg. 2022:1945998221097656. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35503739.
19. Gottlieb M, Long B. Dermatologic manifestations and complications of COVID-19. Am J Emerg Med. 2020;38(9):1715-1721. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32731141.
20. Campbell JI, Dubois MM, Savage TJ, et al. Comorbidities associated with hospitalization and progression among adolescents with symptomatic coronavirus disease 2019. J Pediatr. 2022;245:102-110 e102. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35240138.
21. Shi DS, Whitaker M, Marks KJ, et al. Hospitalizations of children aged 5–11 years with laboratory-confirmed COVID-19 - COVID-NET, 14 states, March 2020–February 2022. MMWR Morb Mortal Wkly Rep. 2022;71(16):574-581. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35446827.
22. Martin B, DeWitt PE, Russell S, et al. Characteristics, outcomes, and severity risk factors associated with SARS-CoV-2 infection among children in the US National COVID Cohort Collaborative. JAMA Netw Open. 2022;5(2):e2143151. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35133437.
23. Kompaniyets L, Agathis NT, Nelson JM, et al. Underlying medical conditions associated with severe COVID-19 illness among children. JAMA Netw Open. 2021;4(6):e2111182. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34097050.
24. Marks KJ, Whitaker M, Anglin O, et al. Hospitalizations of children and adolescents with laboratory-confirmed COVID-19 - COVID-NET, 14 states, July 2021–January 2022. MMWR Morb Mortal Wkly Rep. 2022;71(7):271-278. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35176003.
25. Wang L, Berger NA, Kaelber DC, Davis PB, Volkow ND, Xu R. Incidence rates and clinical outcomes of SARS-CoV-2 infection with the Omicron and Delta variants in children younger than 5 years in the U.S. JAMA Pediatr. 2022;176(8):811-813. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35363246.
26. Karmen-Tuohy S, Carlucci PM, Zervou FN, et al. Outcomes among HIV-positive patients hospitalized with COVID-19. J Acquir Immune Defic Syndr. 2020;85(1):6-10. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32568770.
27. Patel VV, Felsen UR, Fisher M, et al. Clinical outcomes and inflammatory markers by HIV serostatus and viral suppression in a large cohort of patients hospitalized with COVID-19. J Acquir Immune Defic Syndr. 2021;86(2):224-230. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33433966.
28. Sigel K, Swartz T, Golden E, et al. Coronavirus 2019 and people living with human immunodeficiency virus: outcomes for hospitalized patients in New York City. Clin Infect Dis. 2020;71(11):2933-2938. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32594164.
29. Stoeckle K, Johnston CD, Jannat-Khah DP, et al. COVID-19 in hospitalized adults with HIV. Open Forum Infect Dis. 2020;7(8):ofaa327. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32864388.
30. Vizcarra P, Perez-Elias MJ, Quereda C, et al. Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort. Lancet HIV. 2020;7(8):e554-e564. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32473657.
31. Western Cape Department of Health in collaboration with the National Institute for Communicable Diseases, South Africa. Risk factors for coronavirus disease 2019 (COVID-19) death in a population cohort study from the Western Cape Province, South Africa. Clin Infect Dis. 2021;73(7):e2005-e2015. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32860699.
32. Bhaskaran K, Rentsch CT, MacKenna B, et al. HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform. Lancet HIV. 2021;8(1):e24-e32. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33316211.
33. Geretti AM, Stockdale AJ, Kelly SH, et al. Outcomes of coronavirus disease 2019 (COVID-19) related hospitalization among people with human immunodeficiency virus (HIV) in the ISARIC World Health Organization (WHO) Clinical Characterization Protocol (UK): a prospective observational study. Clin Infect Dis. 2021;73(7):e2095-e2106. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33095853.
34. Dandachi D, Geiger G, Montgomery MW, et al. Characteristics, comorbidities, and outcomes in a multicenter registry of patients with human immunodeficiency virus and coronavirus disease 2019. Clin Infect Dis. 2021;73(7):e1964-e1972. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32905581.
35. Hoffmann C, Casado JL, Harter G, et al. Immune deficiency is a risk factor for severe COVID-19 in people living with HIV. HIV Med. 2021;22(5):372-378. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33368966.
36. Tesoriero JM, Swain CE, Pierce JL, et al. COVID-19 outcomes among persons living with or without diagnosed HIV infection in New York State. JAMA Netw Open. 2021;4(2):e2037069. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33533933.
37. Sun J, Patel RC, Zheng Q, et al. COVID-19 disease severity among people with HIV infection or solid organ transplant in the United States: a nationally-representative, multicenter, observational cohort study. medRxiv. 2021. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34341798.
38. Bertagnolio S, Thwin SS, Silva R, et al. Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19. Lancet HIV. 2022;9(7):e486-e495. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35561704.
39. Laracy J, Zucker J, Castor D, et al. HIV-1 infection does not change disease course or inflammatory pattern of SARS-CoV-2-infected patients presenting at a large urban medical center in New York City. Open Forum Infect Dis. 2021;8(2):ofab029. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33604406.
40. Spinelli MA, Brown LB, Glidden DV, et al. SARS-CoV-2 incidence, testing rates, and severe COVID-19 outcomes among people with and without HIV. AIDS. 2021;35(15):2545-2547. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34870933.
41. Yendewa GA, Perez JA, Schlick K, Tribout H, McComsey GA. Clinical features and outcomes of coronavirus disease 2019 among people with human immunodeficiency virus in the United States: a multicenter study from a large global health research network (TriNetX). Open Forum Infect Dis. 2021;8(7):ofab272. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34435074.
42. Yang X, Sun J, Patel RC, et al. Associations between HIV infection and clinical spectrum of COVID-19: a population level analysis based on U.S. National COVID Cohort Collaborative (N3C) data. Lancet HIV. 2021;8(11):e690-e700. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34655550.
43. Nomah DK, Reyes-Uruena J, Diaz Y, et al. Sociodemographic, clinical, and immunological factors associated with SARS-CoV-2 diagnosis and severe COVID-19 outcomes in people living with HIV: a retrospective cohort study. Lancet HIV. 2021;8(11):e701-e710. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34655549.
44. Berzosa Sanchez A, Epalza C, Navarro ML, et al. SARS-CoV-2 infection in children and adolescents living with HIV in Madrid. Pediatr Infect Dis J. 2022;41(10):824-826. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35796220.
45. Vanetti C, Trabattoni D, Stracuzzi M, et al. Immunological characterization of HIV and SARS-CoV-2 coinfected young individuals. Cells. 2021;10(11). Available at: https://www.ncbi.nlm.nih.gov/pubmed/34831410.
46. van der Zalm MM, Lishman J, Verhagen LM, et al. Clinical experience with severe acute respiratory syndrome coronavirus 2-related illness in children: hospital experience in Cape Town, South Africa. Clin Infect Dis. 2021;72(12):e938-e944. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33170927.
47. Nachega JB, Sam-Agudu NA, Machekano RN, et al. Assessment of clinical outcomes among children and adolescents hospitalized with COVID-19 in 6 Sub-Saharan African countries. JAMA Pediatr. 2022;176(3):e216436. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35044430.
48. Rinaldi S, S. P, Pallin M, et al. Prevalence, clinical presentation, and SARS CoV-2 seroreactivity among HIV infected adolescents and youth in Miami. Journal of HIV/AIDS & Infectious Diseases. 2022;9(1). Available at: https://jscholarpublishers.com/articles/JAID/Prevalence-Clinical-Presentation.pdf.
49. Kendall EK, Olaker VR, Kaelber DC, Xu R, Davis PB. Association of SARS-CoV-2 infection with new-onset type 1 diabetes among pediatric patients from 2020 to 2021. JAMA Netw Open. 2022;5(9):e2233014. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36149658.
50. Qeadan F, Tingey B, Egbert J, et al. The associations between COVID-19 diagnosis, type 1 diabetes, and the risk of diabetic ketoacidosis: A nationwide cohort from the U.S. using the Cerner Real-World Data. PLoS One. 2022;17(4):e0266809. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35439266.
51. Malone LA, Morrow A, Chen Y, et al. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of postacute sequelae of SARS-CoV-2 infection (PASC) in children and adolescents. PM R. 2022;14(10):1241-1269. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36169159.
52. Stephenson T, Allin B, Nugawela MD, et al. Long COVID (post-COVID-19 condition) in children: a modified Delphi process. Arch Dis Child. 2022;107(7):674-680. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35365499.
53. Kingery JR, Safford MM, Martin P, et al. Health status, persistent symptoms, and effort intolerance one year after acute COVID-19 infection. J Gen Intern Med. 2022;37(5):1218-1225. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35075531.
54. Pujari S, Gaikwad S, Chitalikar A, Dabhade D, Joshi K, Bele V. Long-coronavirus disease among people living with HIV in western India: an observational study. Immun Inflamm Dis. 2021;9(3):1037-1043. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34078004.
55. Peluso MJ, Spinelli MA, Deveau TM, et al. Postacute sequelae and adaptive immune responses in people with HIV recovering from SARS-COV-2 infection. AIDS. 2022;36(12):F7-F16. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35866847.
56. Payne AB, Gilani Z, Godfred-Cato S, et al. Incidence of multisystem inflammatory syndrome in children among U.S. persons infected with SARS-CoV-2. JAMA Netw Open. 2021;4(6):e2116420. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34110391.
57. Dufort EM, Koumans EH, Chow EJ, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med. 2020;383(4):347-358. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32598830.
58. Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383(4):334-346. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32598831.
59. Levy N, Koppel JH, Kaplan O, et al. Severity and incidence of multisystem inflammatory syndrome in children during 3 SARS-CoV-2 pandemic waves in Israel. JAMA. 2022;327(24):2452-2454. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35588048.
60. Holm M, Espenhain L, Glenthoj J, et al. Risk and phenotype of multisystem inflammatory syndrome in vaccinated and unvaccinated Danish children before and during the Omicron wave. JAMA Pediatr. 2022;176(8):821-823. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35675054.
61. Kenney PO, Chang AJ, Krabill L, Hicar MD. Decreased clinical severity of pediatric acute COVID-19 and MIS-C and increase of incidental cases during the Omicron wave in comparison to the Delta wave. Viruses. 2023;15(1). Available at: https://www.ncbi.nlm.nih.gov/pubmed/36680220.
62. Centers for Disease Control and Prevention. Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C). Available at: https://www.cdc.gov/mis/hcp/case-definition-reporting/  
63. U.S. Food and Drug Administration. Coronavirus Disease 2019 (COVID-19) emergency use authorizations for medical devices. Available at: https://www.fda.gov/medical-devices/emergency-use-authorizations-medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices.
64. Long QX, Liu BZ, Deng HJ, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020;26(6):845-848. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32350462.
65. Xiang F, Wang X, He X, et al. Antibody detection and dynamic characteristics in patients with coronavirus disease 2019. Clin Infect Dis. 2020;71(8):1930-1934. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32306047.
66. Clase CM, Fu EL, Joseph M, et al. Cloth masks may prevent transmission of COVID-19: an evidence-based, risk-based approach. Ann Intern Med. 2020;173(6):489-491. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32441991.
67. Bahl P, Bhattacharjee S, de Silva C, Chughtai AA, Doolan C, MacIntyre CR. Face coverings and mask to minimise droplet dispersion and aerosolisation: a video case study. Thorax. 2020;75(11):1024-1025. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32709611.
68. Centers for Disease Control and Prevention. Use and care of masks. Available at: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/about-face-coverings.html.
69. Centers for Disease Control and Prevention. Isolation and precautions for people with COVID-19. Available at: https://archive.cdc.gov/www_cdc_gov/coronavirus/2019-ncov/your-health/isolation.html
70. Centers for Disease Control and Prevention. Respiratory virus guidance. 2024. Available at: https://www.cdc.gov/respiratory-viruses/guidance/. 
71. Centers for Disease Control and Prevention. Interim infection prevention and control recommendations for healthcare personnel during the coronavirus disease 2019 (COVID-19) pandemic. Available at: https://www.cdc.gov/covid/hcp/infection-control/.
72. Fowlkes AL, Yoon SK, Lutrick K, et al. Effectiveness of 2-dose BNT162b2 (Pfizer BioNTech) mRNA vaccine in preventing SARS-CoV-2 infection among children aged 5–11 years and adolescents aged 12–15 years – PROTECT Cohort, July 2021–February 2022. MMWR Morb Mortal Wkly Rep. 2022;71(11):422-428. Available at: https://pubmed.ncbi.nlm.nih.gov/35298453.
73. Klein NP, Stockwell MS, Demarco M, et al. Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA vaccination in preventing COVID-19-associated emergency department and urgent care encounters and hospitalizations among nonimmunocompromised children and adolescents aged 5–17 years - VISION Network, 10 states, April 2021–January 2022. MMWR Morb Mortal Wkly Rep. 2022;71(9):352-358. Available at: https://pubmed.ncbi.nlm.nih.gov/35239634.
74. Price AM, Olson SM, Patel MM. BNT162b2 Protection against the Omicron variant in children and adolescents. N Engl J Med. 2022. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35544367.
75. Anderson EJ, Creech CB, Berthaud V, et al. Evaluation of mRNA-1273 vaccine in children 6 months to 5 years of age. N Engl J Med. 2022;387(18):1673-1687. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36260859.
76. Zambrano LD, Newhams MM, Olson SM, et al. BNT162b2 mRNA vaccination against coronavirus disease 2019 is associated with a decreased likelihood of multisystem inflammatory syndrome in children aged 5–18 years–United States, July 2021 – April 2022. Clin Infect Dis. 2022. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35924406.
77. Walter EB, Talaat KR, Sabharwal C, et al. Evaluation of the BNT162b2 Covid-19 vaccine in children 5 to 11 years of age. N Engl J Med. 2022;386(1):35-46. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34752019.
78. Creech CB, Anderson E, Berthaud V, et al. Evaluation of mRNA-1273 Covid-19 vaccine in children 6 to 11 years of age. N Engl J Med. 2022;386(21):2011-2023. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35544369.
79. Fleming-Dutra KE, Britton A, Shang N, et al. Association of prior BNT162b2 COVID-19 vaccination with symptomatic SARS-CoV-2 infection in children and adolescents during Omicron predominance. JAMA. 2022;327(22):2210-2219. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35560036.
80. Cohen-Stavi CJ, Magen O, Barda N, et al. BNT162b2 Vaccine effectiveness against Omicron in children 5 to 11 years of age. N Engl J Med. 2022;387(3):227-236. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35767475.
81. Tan SHX, Cook AR, Heng D, Ong B, Lye DC, Tan KB. Effectiveness of BNT162b2 vaccine against Omicron in children 5 to 11 years of age. N Engl J Med. 2022;387(6):525-532. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35857701.
82. Sacco C, Del Manso M, Mateo-Urdiales A, et al. Effectiveness of BNT162b2 vaccine against SARS-CoV-2 infection and severe COVID-19 in children aged 5–11 years in Italy: a retrospective analysis of January–April, 2022. Lancet. 2022;400(10346):97-103. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35780801.
83. Amir O, Goldberg Y, Mandel M, et al. Initial protection against SARS-CoV-2 omicron lineage infection in children and adolescents by BNT162b2 in Israel: an observational study. Lancet Infect Dis. 2023;23(1):67-73. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36096146.
84. Levy M, Recher M, Hubert H, et al. Multisystem inflammatory syndrome in children by COVID-19 vaccination status of adolescents in France. JAMA. 2022;327(3):281-283. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34928295.
85. Munoz FM, Sher LD, Sabharwal C, et al. Evaluation of BNT162b2 COVID-19 vaccine in children younger than 5 years of age. N Engl J Med. 2023;388(7):621-634. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36791162.
86. Regan JJ, Moulia DL, Link-Gelles R, et al. Use of updated COVID-19 vaccines 2023–2024 formula for persons aged >/=6 months: recommendations of the Advisory Committee on Immunization Practices – United States, September 2023. MMWR Morb Mortal Wkly Rep. 2023;72(42):1140-1146. Available at: https://www.ncbi.nlm.nih.gov/pubmed/37856366.
87. 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.
88. DeCuir J, Surie D, Zhu Y, et al. Effectiveness of monovalent mRNA COVID-19 vaccination in preventing COVID-19-associated invasive mechanical ventilation and death among immunocompetent adults during the Omicron variant period – IVY Network, 19 U.S. states, February 1, 2022–January 31, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(17):463-468. Available at: https://www.ncbi.nlm.nih.gov/pubmed/37104244.
89. Centers for Disease Control and Prevention. Use of COVID-19 vaccines in the United States. Available at: https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html.
90. Halasa NB, Olson SM, Staat MA, et al. Maternal vaccination and risk of hospitalization for Covid-19 among infants. N Engl J Med. 2022;387(2):109-119. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35731908.
91. Cambou MC, Liu CM, Mok T, et al. Longitudinal evaluation of antibody persistence in mother–infant dyads after severe acute respiratory syndrome coronavirus 2 infection in pregnancy. J Infect Dis. 2023;227(2):236-245. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36082433.
92. Brumme ZL, Mwimanzi F, Lapointe HR, et al. Humoral immune responses to COVID-19 vaccination in people living with HIV receiving suppressive antiretroviral therapy. NPJ Vaccines. 2022;7(1):28. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35228535.
93. Levy I, Wieder-Finesod A, Litchevsky V, et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in people living with HIV-1. Clin Microbiol Infect. 2021;27(12):1851-1855. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34438069.
94. Noe S, Ochana N, Wiese C, et al. Humoral response to SARS-CoV-2 vaccines in people living with HIV. Infection. 2022;50(3):617-623. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34694595.
95. Ruddy JA, Boyarsky BJ, Bailey JR, et al. Safety and antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in persons with HIV. AIDS. 2021;35(14):2399-2401. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34261097.
96. Chammartin F, Kusejko K, Pasin C, et al. Determinants of antibody response to severe acute respiratory syndrome coronavirus 2 mRNA vaccines in people with HIV. AIDS. 2022;36(10):1465-1468. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35876706.
97. Frater J, Ewer KJ, Ogbe A, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial. Lancet HIV. 2021;8(8):e474-e485. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34153264.
98. Woldemeskel BA, Karaba AH, Garliss CC, et al. The BNT162b2 mRNA vaccine elicits robust humoral and cellular immune responses in people living with human immunodeficiency virus (HIV). Clin Infect Dis. 2022;74(7):1268-1270. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34293114.
99. Xu X, Vesterbacka J, Aleman S, Nowak P, Group CS. High seroconversion rate after vaccination with mRNA BNT162b2 vaccine against SARS-CoV-2 among people with HIV - but HIV viremia matters? AIDS. 2022;36(3):479-481. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35084386.
100. Nault L, Marchitto L, Goyette G, et al. Covid-19 vaccine immunogenicity in people living with HIV-1. Vaccine. 2022;40(26):3633-3637. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35568588.
101. Liu Y, Han J, Li X, et al. COVID-19 vaccination in people living with HIV (PLWH) in China: a cross sectional study of vaccine hesitancy, safety, and immunogenicity. Vaccines (Basel). 2021;9(12). Available at: https://www.ncbi.nlm.nih.gov/pubmed/34960204.
102. Hassold N, Brichler S, Ouedraogo E, et al. Impaired antibody response to COVID-19 vaccination in advanced HIV infection. AIDS. 2022;36(4):F1-F5. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35013085.
103. Shimabukuro T. Update on myocarditis following mRNA COVID-19 vaccination. Presented at Advisory Committee on Immunization Practices; 2022. Available at: https://www.fda.gov/media/159228/download. 
104. Block JP, Boehmer TK, Forrest CB, et al. Cardiac Complications after SARS-CoV-2 infection and mRNA COVID-19 vaccination – PCORnet, United States, January 2021–January 2022. MMWR Morb Mortal Wkly Rep. 2022;71(14):517-523. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35389977.
105. S. Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization of pemgarda (Pemivibart). 2024. Available at: https://www.fda.gov/media/177067/download?attachment
106. A study to investigate the prevention of COVID-19 with VYD222 in adults with immune compromise and in participants aged 12 years or older who are at risk of exposure to SARS-CoV-2. Clinical Trials.gov identifier: NCT06039449. Updated May 31, 2024. Available at: https://clinicaltrials.gov/study/NCT06039449#more-information
107. 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.
108. Rajme-Lopez S, Martinez-Guerra BA, Zalapa-Soto J, et al. Early outpatient treatment with remdesivir in patients at high risk for severe COVID-19: a prospective cohort study. Open Forum Infect Dis. 2022;9(10):ofac502. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36285176.
109. Ader F, Bouscambert-Duchamp M, Hites M, et al. Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial. Lancet Infect Dis. 2022;22(2):209-221. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34534511.
110. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395(10236):1569-1578. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32423584.
111. WHO Solidarity Trial Consortium, Pan H, Peto R, et al. Repurposed antiviral drugs for Covid-19 – interim WHO solidarity trial results. N Engl J Med. 2021;384(6):497-511. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33264556.
112. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19 – final report. N Engl J Med. 2020;383(19):1813-1826. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32445440.
113. Ahmed A, Rojo P, Agwu A, et al. Remdesivir treatment for COVID-19 in hospitalized children: CARAVAN interim results. Presented at Conference on Retroviruses and Oppportunistic Infections; 2022. Virtual. Available at: https://www.croiconference.org/abstract/remdesivir-treatment-for-covid-19-in-hospitalized-children-caravan-interim-results.
114. Goldman DL, Aldrich ML, Hagmann SHF, et al. Compassionate use of remdesivir in children with severe COVID-19. Pediatrics. 2021;147(5). Available at: https://www.ncbi.nlm.nih.gov/pubmed/33883243.
115. Mendez-Echevarria A, Perez-Martinez A, Gonzalez Del Valle L, et al. Compassionate use of remdesivir in children with COVID-19. Eur J Pediatr. 2021;180(4):1317-1322. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33200304.
116. Schuster JE, Halasa NB, Nakamura M, et al. A description of COVID-19-directed therapy in children admitted to U.S. intensive care units 2020. J Pediatric Infect Dis Soc. 2022;11(5):191-198. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35022779.
117. The University of Liverpool. COVID-19 drug interactions. 2023. Available at: https://www.covid19-druginteractions.org
118. 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.
119. EPIC-Peds: A Study to Learn About the Study Medicine Called PF-07321332 (Nirmatrelvir)/Ritonavir in Patients Under 18 Years of Age With COVID-19 That Are Not Hospitalized But Are at Risk for Severe Disease. Clinical Trials.gov identifier: NCT05261139. Updated June 4, 2024. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05261139?term=NCT05261139&draw=2&rank=1
120. Vora SB, Englund JA, Trehan I, et al. Monoclonal antibody and antiviral therapy for mild-to-moderate COVID-19 in pediatric patients. Pediatr Infect Dis J. 2023;42(1):32-34. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36476522.
121. Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization for paxlovid. 2023. Available at: https://www.fda.gov/media/155050/download.
122. Infectious Diseases Society of America and HIV Medicine Association. Paxlovid for the treatment of COVID-19: considerations for people with HIV and hepatitis C, version 12/19/2022. 2022. Available at: https://www.idsociety.org/globalassets/covid-19-real-time-learning-network/patient-populations/hiv/oral-covid-tx-considerations-for-people-with-hiv-and-hcv.pdf.
123. CDC Health Alert Network. COVID-19 rebound after paxlovid treatment. 2022. Available at: https://emergency.cdc.gov/han/2022/pdf/CDC_HAN_467.pdf.
124. Group RC, Horby P, Lim WS, et al. 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.
125. Food and Drug Administration. Fact sheet for healthcare providers emergency use authorization (EUA) of baricitinib. 2022. Available at: https://www.fda.gov/media/143823/download.
126. Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization for actemra. 2021. Available at: https://www.fda.gov/media/150321/download.
127. Whitworth H, Sartain SE, Kumar R, et al. Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C. Blood. 2021;138(2):190-198. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33895804.
128. Aguilera-Alonso D, Murias S, Martinez-de-Azagra Garde A, et al. Prevalence of thrombotic complications in children with SARS-CoV-2. Arch Dis Child. 2021;106(11):1129-1132. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33931403.