key: cord-0991755-e5p7qqrg
authors: Connelly, James A.; Chong, Hey; Esbenshade, Adam J.; Frame, David; Failing, Christopher; Secord, Elizabeth; Walkovich, Kelly
title: Impact of COVID-19 on Pediatric Immunocompromised Patients
date: 2021-05-26
journal: Pediatr Clin North Am
DOI: 10.1016/j.pcl.2021.05.007
sha: 4693348ce3867ae19f4cfa83e5e25420ea7f059f
doc_id: 991755
cord_uid: e5p7qqrg

Although living with the threat of severe infection is a constant worry for many pediatric immunocompromised patients, the pandemic begotten by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) created new fears and challenges for families and health care providers. As people around the world through government directive or independent choice moved into protective isolation, immunosuppressed children who routinely require medical management were challenged with necessary public ventures to health care facilities. Medical centers adapted by developing new approaches to care for immunocompromised children such as expanding telemedicine services and conversion to at home immune therapies to reduce infectious exposure. Testing for SARS-CoV-2 of asymptomatic patients prior to medical therapies became routine in most modern health care units and development of highly sensitive assays was critical to avoid patient and staff exposure as well as initiation of new immunosuppressive treatment in positive patients. As the prevalence of coronavirus disease (COVID-19) amplified and infected immunocompromised patients became more common, questions quickly arose including how aggressively to treat the infection with most agents still in clinical trials. Additionally how should chronic immunosuppressant drugs that may interfere with the ability to clear the virus be adjusted? Finally, what if the infection leads to excessive immune responses or flares of the underlying disorder? In this review, we explore the impact of the COVID-19 pandemic on immunocompromised children during the first year, summarizing what is known and yet to be discovered, approaches to testing and treatment of SARS-CoV-2, considerations in management of underlying immune suppressive medications, outcomes published to date, and strategies for vaccinating this unique population.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused critical coronavirus disease most often in the elderly and individuals with co-morbid medical conditions. Although growing evidence supports the importance of an intact innate immune response at the onset of viral infection, mortality caused by dysregulated immune responses, particularly in adults, has shown a spotlight on the delicate balance of a robust, but coordinated and controlled immune activity against infection 1 Additionally, this publication will examine questions commonly faced amongst health care providers including how to test for SARS-CoV-2 with high sensitivity, how to treat active SARS-CoV-2 J o u r n a l P r e -p r o o f infection in immunocompromised youth, how to consider the safety and efficacy of COVID vaccine for the immunocompromised, and how to provide medical and psychosocial support while reducing infectious exposure in immunocompromised children. The outcomes of SARS-CoV-2 in immunocompromised patients to date is also reviewed. Lessons learned caring for immunocompromised children during the pandemic, including some unforeseen benefits of the lockdown, are presented as valuable education for providers caring for both healthy and sick children.

Despite the potential for an altered immune response to SARS-CoV-2, asymptomatic presentations are common in pediatric immunocompromised patients (13-62% in published cohorts, see Table 1 ), emphasizing that the lack of signs and symptoms does not rule out infection. However, identifying SARS-CoV-2 infection is especially important in patients with immune deficits, where decisions on admission, treatment and procedures may be dependent on ruling out acute infection.

Additionally, given that many immunocompromised children receive care in proximity to other immunocompromised patients in infusion centers or inpatient wards, using high-sensitivity testing is critical to curb exposures.

To that end, the Infectious Disease Society of America (IDSA), in recommendations from January 2021, 3 specifically recommends SARS-CoV-2 RNA testing in asymptomatic immunocompromised patients being admitted to the hospital and before hematopoietic stem cell (HSCT) or solid organ transplant (SOT) regardless of COVID-19 exposure history or community SARS-CoV-2 infection rate 4, 5, 6 . This recommendation was based on the presumed risk of nosocomial transmission, although data is limited 7 . Of note, the IDSA guidelines specifically include cytotoxic chemotherapy, biologic or cellular therapy, high-dose steroids and SOT or HSCT. There is no inclusion of patients with primary immunodeficiency, immune dysregulatory disorders or HIV under the "immunocompromised patients," but biologically their immune deficits are similar. For J o u r n a l P r e -p r o o f asymptomatic outpatients receiving chemotherapy or other immunosuppressive medications for autoimmune disease, the IDSA recommends that the decision for testing prior to therapy be individualized as there remains a significant evidence gap to reliably guide practice.

It is important to note that numerous tests to detect the SARS-CoV-2 virus have emergency use authorization (EUA) and that their sensitivities and turn-around times are not uniform 3, 8 . These assays detect parts of the virus via RNA or antigen testing and molecular analysis can be completed via rapid reverse transcription polymerase chain reaction (RT-PCR) (sensitivity 98%, specificity 97%, 45-60 minutes for test completion), standard lab-based nucleic acid amplification testing (NAAT) (sensitivity 98%, specificity 97%) or rapid isothermal NAAT (sensitivity 81%, specificity 99%, 5-15 minutes for test completion) testing 3 . Thus, providers should appreciate the potential for false negative testing from rapid bedside testing, which may be less sensitive and miss asymptomatic patients as they are frequently completed via rapid isothermal NAAT. Beyond assay limitations, specimen inadequacy (e.g. tentatively swabbing the nasopharynx of patients with thrombocytopenia) and timing of collection relative to the onset of symptoms can contribute to false negative tests 8 .

Serology testing is also available to detect past SARS-CoV-2 infection, but the utility of the test is unknown in patients with humoral immune defects who may fail to seroconvert as the assays rely on detection of anti-SARS-CoV-2 IgG, IgM, IgA or total antibody. Additionally, as immunoglobulin replacement products begin to include anti-SARS-CoV-2 IgG, the value of serologic detection will be unclear for patients on replacement therapy. Standard IDSA approaches for the use of serologic testing for SARS-CoV-2 infection should be followed for immunocompromised pediatric patients 9 .

Understanding the infectivity rate of SARS-CoV-2 has been a huge epidemiologic undertaking.

In theory, immunocompromised children may be less likely to contract SARS-CoV-2 secondary to J o u r n a l P r e -p r o o f already ingrained infection prevention techniques, e.g. hand washing and social isolation. However, interaction with the health care system may raise the risk of a positive contact as demonstrated in a Madrid study in which 4 of 15 cases (27%) of SARS-CoV-2 infections in pediatric oncology patients were traced to nosocomial exposure 10 . Comparison of infectivity rates with healthy children is difficult secondary to discrepancies in testing practices in immunocompromised patients who are more likely to undergo testing over concerns of developing severe COVID-19 or as a screen prior to hospital admissions, surgical procedures, or receiving chemotherapy. Therefore, immunocompromised children are more likely to be screened when asymptomatic, theoretically falsely raising the relative prevalence of SARS-CoV-2 in this population compared to immunocompetent children.

In review of the current 13 manuscripts that detailed their testing strategy for pediatric oncology patients, just one cohort limited SARS-CoV-2 testing to symptomatic patients only 11 .

Interestingly, this strategy was adopted in Mexico where resources for broad testing are limited, indicating that studies in poorly-resourced countries may also underestimate the prevalence secondary to less aggressive screening. Amongst pediatric oncology hospitals in New York and New Jersey, the positivity rate at the height of the pandemic was 16.95% with 32.7% of the cases being identified in asymptomatic patients 12 . Symptomatic patients were also more likely to be tested early in the pandemic as demonstrated in a single center study at the UPMC Children's Hospital of Pittsburgh where immunocompromised pediatric patients with fever or respiratory symptoms were 3-times (58.0% versus 19.5%) as likely to be tested for SARS-CoV-2 in comparison to immunocompetent patients 10 . It is important to note that testing strategies continue to evolve as changes in disease prevalence and access to test supplies have fluctuated and these early reports may not reflect current screening practices.

Another strategy to evaluate the burden of SARS-CoV-2 is to assess seroprevalence in pediatric cohorts. The UPMC Children's Hospital of Pittsburgh tested for the presence of SARS-CoV-J o u r n a l P r e -p r o o f 8 2 IgG in convenience blood samples from immunocompromised and general pediatric patients 10 . In 485 immunocompromised patients, 1% were found to have IgG antibodies to SARS-CoV-2 spike protein, which was similar to the immunocompetent cohort (0.6%). Seroprevalence was highest in rheumatology (4.3%) and SOT (1.9%), with no detection of antibodies in HSCT, primary immunodeficiency, or inflammatory bowel disease (IBD) patients, although this data may underestimate the true prevalence given the possibility of poor humoral response to SARS-CoV-2 in some immunocompromised patients.

As of March 1, 2021, 2,617 patients have met the case definition of MIS-C in the United States 13 . Estimating the prevalence of MIS-C in immunocompromised patients may prove more difficult as unlike SARS-CoV-2, MIS-C does not have specific testing but requires a constellation of symptoms and laboratory evidence of inflammation for diagnosis that may overlap with the underlying disorder, especially in rheumatology patients. MIS-C has been diagnosed in patients with underlying IBD, but presenting features including fever, gastrointestinal disease, mouth ulcers, and elevation of inflammatory markers are common manifestations of both conditions 14, 15, 16 . MIS-C, therefore, has the potential to be both under-and over-diagnosed in immunocompromised patients and may require more specific findings such as Kawasaki-like features to confirm a MIS-C diagnosis.

Despite a large number of therapeutic studies related to COVID-19 being done over the past year, the majority of participants are immunocompetent adults 17, 18 . As such, treatment of immunocompromised patients mirrors that of immunocompetent patients. At the time of this publication, remdesivir, a nucleoside analog that when incorporated into RNA inhibits the replication of SARS-CoV-2 by causing delayed chain termination, is the only agent with FDA approval for COVID-19 treatment. Remdesivir is approved for hospitalized patients (aged ≥12 years and weighing J o u r n a l P r e -p r o o f ≥40 kg) requiring supplemental oxygen 19, 17, 20 and through an emergency use authorization (EUA) for hospitalized children weighing ≥ 3.5 kg. Currently there is insufficient data for use in non-hospitalized mild to moderate cases or for non-oxygen requiring hospitalized patients, with argument that remdesivir should be considered in these situations for immunocompromised patients. For hospitalized adult patients, dexamethasone afforded a survival benefit in patients receiving respiratory support and led to increased ventilator-free days in mechanically ventilated patients 21, 22 .

Dexamethasone in combination with remdesivir may be considered for immunocompromised patients with severe or critical COVID-19 requiring respiratory support but must be balanced with the risk for inadequate viral control and secondary infections.

Immunocompromised patients who have decreased ability or inability to make antibodies may be at risk for prolonged illness with decreased capacity to clear the virus 23 . While no specific trials have been reported in this population, two therapies that could be considered are anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma. Currently, the FDA has issued an EUA for the anti-SARS-CoV-2 monoclonal antibodies bamlanivimab 24 , bamlanivimab plus etesevimab 25 , and casirivimab plus imdevimab 26 for non-hospitalized adult and pediatric patients (≥12 years and weighing ≥40 kg), who are at high risk for disease progression or hospitalization, including those with immunosuppressive disorders or those receiving immunosuppressive treatment. Convalescent plasma from recovered COVID-19 donors also received an EUA from the FDA for hospitalized patients early in the course of disease and those hospitalized with impaired humoral immunity 27, 28 .

This recommendation, however, is not fully supported by pediatric subspecialist groups who have advocated against routine administration of monoclonal antibodies for COVID-19 treatment due to the lack of evidence for safety and efficacy in children 29 .

As demonstrated in Table 1 others (e.g. tocilizumab, dexamethasone) 33, 21 have been attempted to control dysregulated immune responses in severe COVID-19. This dilemma has led physicians to perform an individualized riskbenefit evaluation to weigh the risk of reducing immunosuppression against the risk of disease flare or worsening disease activity which potentially could have both devastating short and long-term consequences 34 . Thankfully, guidance in pediatric immunocompromised patient care is developing as our experience in COVID-19 expands. For example, the current recommendation for pediatric cancer patients with SARS-CoV-2 infections is to avoid major alterations in underlying therapy unless there is evidence of severe COVID-19 infection 35 .

At the onset of the COVID-19 pandemic, it was assumed that poor anti-viral immunity in immunocompromised patients would place them at high risk for complications as seen for other J o u r n a l P r e -p r o o f respiratory viruses including influenza, RSV, and common strains of human coronavirus (OC43, NL63, HKU1, and 229E) 36, 37, 38 . However, immunocompromised status and poor outcomes has not been reported during the SARS-CoV-1 and MERS-CoV epidemics 1 . This somewhat paradoxical observation may stem from the unique immune pathology induced by SARS-CoV-2. The usual immune response to SARS-CoV-2 is an initial innate immune response through type I interferons followed by an adaptive humoral and cellular immune response 39 . Although adequate immune function is necessary to control SARS-CoV-2 infection, significant toxicity and death are often a sequelae of inappropriate and dysregulated immune responses and not a direct consequence of viral invasion and replication 40 . This has raised the intriguing possibility that patients with primary or secondary immune defects may not be at increased risk of death from COVID-19, but also that certain subsets of patients may be protected from severe disease by their inability to mount a pathologic immune response to SARS-CoV-2 41 .

Initial studies in adults, however, have demonstrated that oncology and SOT patients are at higher risk for severe outcomes including intubation and death from COVID-19 42, 43, 44 . In contrast, IBD and rheumatology adult patients taking biologics and JAK inhibitors displayed no increased incidence of severe disease 45, 46 . The difference in outcomes may be related to the type and degree of immune suppression, but comorbidities such as hypertension, heart disease, diabetes, and chronic kidney disease were also highly prevalent in adult cancer and SOT patients with severe COVID-19 42 .

Clinical outcomes in immunocompetent children with COVID-19 are superior to adults and several mechanisms including lower angiotensin converting enzyme (ACE)-2 expression, enhanced immune tolerance, and fewer co-morbidities have been proposed as reasons for the discrepant outcomes 47 . These protective features may be minimized in some immunocompromised populations as ACE-2 can be overexpressed in some patients with IBD and systemic lupus erythematous J o u r n a l P r e -p r o o f (SLE) 48, 49 . Additionally, immune tolerance mechanisms may be disrupted by inborn errors of immunity such as pathogenic variants in FOXP3 or CTLA4, and co-morbidities exist due to the underlying genetic defect or toxicities related to treatment or prior infection 49 . Children may also be on relatively higher doses of immune suppression in comparison to adults for some conditions such as SOT and therefore COVID-19 outcome trends seen in immunosuppressed adults may not be translatable to pediatrics 50 .

A summary of currently published studies on pediatric immunocompromised cohorts is provided in Table 1 , permitting some interesting early observations. First, in pediatric oncology patients, the risk of death is less than adults, but appears to be higher than the general pediatric population and may be worse when compounded by certain high-risk demographics, e.g. male, obese, and older age, or in patients with hematologic malignancies 12,51-54 . In contrast to oncology patients, published cohorts of pediatric rheumatology patients, SOT, chronic kidney disease on immune suppression, and IBD reported low rates of severe complications, but the literature is less extensive in these diseases. COVID-19 severity in patients with inborn errors of immunity is dependent on the underlying defect. Although there is potential for reporter bias, complete absence of adaptive immunity appears lethal with mortality from COVID-19 in all reported severe combined immunodeficiency (SCID)

patients not yet transplanted in an Iranian case series that included 3 patients with SCID and 1 patient with Omenn syndrome 55 . However, pediatric patients with non-severe defects in adaptive immunity presented with asymptomatic or mild COVID-19 disease in a global (14 patients) and Israeli (9 patients) survey of medical providers 40, 41 . Despite the concern for excessive immune activation in auto-inflammatory disorders, severe disease has not been frequently reported and may be a misguided concern or the inflammation is well attenuated by preventive immunosuppression in these J o u r n a l P r e -p r o o f patients 41 . A similar concern is whether MIS-C will be more prevalent or severe in patients with autoinflammatory disorders, but it is too early to speculate as only a few anecdotal cases of MIS-C in patients with immune disorders are published to date [14] [15] [16] 41 .

Overall, the clinical course in immunocompromised patients with SARS-CoV-2 is favorable, but some caution is warranted in caring for these patients. First, based on recent data demonstrating the importance of type I interferons in initial SARS-CoV-2 control, patients who have severely deficient type I interferon signaling or immune disorders, e.g. secondary to Toll-like receptor 3 (TLR3) or interferon regulatory factor 7 (IRF7) defects, or those that predispose to auto-antibodies against type I interferons may be at risk for critical disease 40, 56, 57 . Second, some cases of death have been attributed to concurrent infections or an underlying primary disorder, highlighting the need for continued monitoring for additional infections, disease progression, and immune related adverse events that may be independent or indirectly related to SARS-CoV-2 infection 41 

The COVID-19 pandemic impacted access to care for non-SARS-CoV-2 infected patients as hospital systems scrambled to accommodate the surge of infected patients and limit transmission of infection amongst staff and patients. Unfortunately, the need to implement social distancing protocols, mobilization of SARS-CoV-2 testing, redeployment of providers and reduction in staff, use of critical care beds for severe COVID-19 patients, and parental and patient anxiety of traveling to medical J o u r n a l P r e -p r o o f centers all contributed to delayed access and untoward consequences for some immunocompromised patients. For example, surveyed pediatric rheumatologists indicated one third of patients suffered a delayed diagnosis or joint injections due to lack of access for evaluation and 21.9% had patients who experienced a flare due to delayed appointments 58 reports have yet to describe a rebound of cancer diagnoses, extreme sickness in new cancer patients is documented and these presentation delays to oncology centers have been attributed to parental reluctance to seek medical care, decreased referrals to major medical centers, limitations of telemedicine, and a diagnostic bias towards COVID-19 for presenting signs of a malignancy 61 . A survey of SOT and HSCT centers in Europe reported that 2/3 of centers reduced their transplant activity 62 . However, pediatric kidney transplants in the United States has largely returned to baseline after the initial surge of COVID-19 63 . In the United Kingdom, restrictions on endoscopy procedures resulted in a majority of pediatric patients being diagnosed with "presumed IBD" without histologic confirmation 64 . IBD admissions for new diagnoses and endoscopic re-evaluation were also significantly reduced during the lock down in Italy 65 .

In attempts to maintain access to care while minimizing infectious exposure and conserving personal protective equipment, sub-specialty providers pivoted toward telemedicine 66 Providers, similarly, have turned to pre-pandemic psychosocial service models like those utilized for J o u r n a l P r e -p r o o f people with HIV that have historically utilized home visits, telemedicine and adherence programs inclusive of directly observed therapy, motivational interviewing sessions, and social work checkins 71, 72, 73 . Home delivery of medication was already occurring for many high-risk patients and continuation of this service has minimized treatment gaps for some patients. Unfortunately, the same services have not been available in many resource poor areas of the US and abroad, and services to those with HIV have suffered interruptions of heath care 74, 75, 76 . The same service interruptions may be inferred for other high risk immune deficient patients in poor resource areas.

At the onset of the pandemic, uncertainty over the risk of severe COVID-19, drug shortages for medications utilized for both immunocompromised patients and SARS-CoV-2, and re-allocation of resources to COVID-19 patient care and research led to numerous changes in management of immunocompromised children. Early in the pandemic, pediatric oncologists regularly delayed chemotherapy (48-100% in published cohorts, see Table 1 ), and reports of patient deaths secondary to disease progression while delaying induction or pausing chemotherapy during SARS-CoV-2 infection have been reported. Pediatric oncology clinical trial enrollment decreased as resources were diverted to COVID-19 research, restrictions on research were made in an effort to curb SARS-CoV-2 transmission and research staff furloughed to limit the negative institutional financial impact of COVID-19. As such, some pediatric oncology patients, particularly those with relapsed/refractory disease had less options for therapy due to delays in opening new studies 77 .

In China and South Korea, 20% of pediatric IBD patients suffered disease exacerbation when infliximab infusions were delayed 78 . In the UK, standard treatment with a TNF inhibitor was replaced with exclusive enteral nutrition for new IBD patients as diagnosis could not be confirmed secondary to reduction in endoscopy procedures 64 Additionally, drug shortages forced changes in management and mandated strategic planning to preserve doses for critical care 82 . In pediatric and adult rheumatology, many patients receiving IV tocilizumab were switched to the SQ form as the supply of IV tocilizumab was consumed for treatment of severe COVID-19. This switch to SQ tocilizumab resulted in patient/parent anxiety of the risk of disease flare or worsening disease activity even though switching to subcutaneous route has been found to be effective alternative for children with juvenile idiopathic arthritis 83 . Other drugs, e.g.

hydroxychloroquine, demonstrated a huge surge in prescriptions early in the pandemic presumably attributed to off-label use for COVID-19 treatment raising concern for decreased availability of the drug for SLE or other autoimmune indications 84, 85, 86 .

With concerns for nosocomial exposure, providers prioritized home administered therapeutic options when possible, particularly for immunocompromised patients. The National Institute for Health and Care Excellence (NICE) published COVID-19 rapid guidelines specifically recommending clinicians to consider switching intravenous (IV) medications to subcutaneous (SQ) form to minimize exposure of SARS-CoV-2. Anecdotally, children receiving IgG replacement were transitioned from IV IgG in hospital infusion areas to either SQ or at home IV IgG and when feasible, and outpatient chemotherapy regimens were favored, e.g. SQ cytarabine versus IV vinblastine with prednisone for children with Langerhans cell histiocytosis given the success of cytarabine monotherapy in refractory disease 87 . 93 . The vector shuttles the gene into the nucleus of the cell where it is transcribed and translated into the spike protein, but the genetic material does not integrate into host DNA and because the vector does not replicate it cannot cause human disease 99 . Therefore, as all 3 vaccines cannot result in infection, they are likely safe for patients with immunodeficiency. However, live attenuated COVID-19 vaccines are in development or clinical trials, so in the future it will be important to know which vaccine is being offered with the live attenuated vaccines being avoided until work up and discussion with an immunologist 100 . Another theoretical concern is administration of vaccines in patients with autoimmune and autoinflammatory disorders with excessive production of inflammatory cytokines in response to viral products. However, given the risk of SARS-CoV-2 infection in these disorders, the immunology community has provided cautious support for vaccination in these patients and ideally should be administered during periods of low disease activity 101 .

In addition to safety concerns, efficacy of these vaccines is unclear and likely variable depending on the immune defect. Classically, antibody production is used as a measure of the protection offered from immunization, but vaccines may generate T-cell responses as well, which could be of benefit in those with humoral defects. Studies examining patients recovered from COVID- From a healthcare perspective, the massive uptake of telemedicine provided an alternative strategy for patients with compromised immune systems to maintain access to care with increased convenience and decreased cost. Given that immunocompromised patients are likely to benefit from continued telehealth options post-pandemic, it is imperative that action be taken to preserve the expansion of compensated telehealth options, while also appreciating that in-person visits are vital for some patients to diagnose new or progressive disease. Additionally, strategies to mitigate barriers for telehealth uptake to improve equity of access as well as parental/patient preferences for care received in-person versus virtually must be explored.

Although global efforts have accelerated our understanding and care of SARS-CoV-2 patients, our knowledge of clinical outcomes and treatment in immunocompromised patients is limited, particularly in inborn errors of immunity and pediatric HIV. Challenges remaining for pediatricians include sustained, global collaboration to consolidate knowledge in these rare patient groups, J o u r n a l P r e -p r o o f continued adaptation of knowledge gained from immunocompetent patients to immunocompromised cohorts, and further study on the safety and efficacy of current and developing vaccines. Persistent advocacy for rare diseases is even more critical as the clinical, scientific, and philanthropic communities remain focused on COVID-19 care and research.

Finally, a comment that immunocompromised parents hear is: "I finally understand what it is like to live like you. I am afraid to get an infection. I cannot just go anywhere I want to go anymore".

Although the COVID-19 pandemic has been difficult for everyone on a personal and professional level, the anxiety of infection and social isolation will persist for immunocompromised families even as the risk of SARS-CoV-2 transmission subsides. It is imperative that we leverage knowledge gained from this pandemic to improve the health and quality of life of immunocompromised children so that they may live without fear.

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Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States

Optimal time between the last methotrexate administration and seasonal influenza vaccination in rheumatoid arthritis: post hoc analysis of a randomised clinical trial

Effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial

COVID-19 vaccination in immunocompromised patients

The Johnson & Johnson Vaccine for COVID-19

COVID-19: Coronavirus Vaccine Development Updates

SARS-CoV-2 vaccines and autoimmune diseases amidst the COVID-19 crisis

COVID-19 vaccine BNT162b1 elicits human antibody and T(H)1 T cell responses

Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults

Social Distancing for COVID-19 and Diagnoses of Other Infectious Diseases in Children

Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment

COVID-19 disease in New York City pediatric hematology and oncology patients

COVID-19 infection in children and adolescents with cancer in Madrid

COVID-19 in pediatric oncology from French pediatric oncology and hematology centers: High risk of severe forms? Pediatr Blood Cancer

COVID-19 in pediatric cancer patients in a resource-limited setting: National data from Peru

Severity of COVID-19 in children with cancer: Report from the United Kingdom Paediatric Coronavirus Cancer Monitoring Project

COVID-19 in Children and Adolescents With Cancer From a Single Center in Mexico City

Management of childhood-onset autoinflammatory diseases during the COVID-19 pandemic

Group tRDE-AW. COVID-19 in Children With Rheumatic Diseases in the Spanish National Cohort EPICO-AEP

SARS-CoV-2 infection in Spanish children with chronic kidney pathologies

The severity of COVID-19 in children on immunosuppressive medication

COVID-19 in children treated with immunosuppressive medication for kidney diseases

Clinical outcome of SARS-CoV-2 infection in immunosuppressed children in Spain

Clinical course of COVID-19 among immunocompromised children: a clinical case series