INTRODUCTION — Coronaviruses are important human and animal pathogens [1]. At the end of 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei province of China. It rapidly spread, resulting in an epidemic throughout China, followed by an increasing number of cases in other countries throughout the world. In February 2020, the World Health Organization (WHO) designated the disease COVID-19, which stands for coronavirus disease 2019 [2]. The virus that causes COVID-19 is designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); previously, it was referred to as 2019-nCoV. The WHO declared COVID-19 a pandemic on March 11, 2020 [3].
Understanding of COVID-19 is evolving. Ongoing guidance has been issued by the WHO and by the United States Centers for Disease Control and Prevention [4,5]. Links to these and other related society guidelines are found elsewhere. (See 'Society guideline links' below.)
This topic will discuss the management of COVID-19 in children. The epidemiology and clinical features of COVID-19 that are specific to children, multisystem inflammatory syndrome in children, and COVID-19 in pregnancy are discussed separately:
●(See "COVID-19: Clinical manifestations and diagnosis in children".)
●(See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) management and outcome".)
●(See "COVID-19: Overview of pregnancy issues".)
●(See "COVID-19: Intrapartum and postpartum issues".)
General aspects of the epidemiology, virology, prevention, and diagnosis of COVID-19 and the management of COVID-19 in adults are discussed separately:
●(See "COVID-19: Epidemiology, virology, and prevention".)
●(See "COVID-19: Vaccines".)
●(See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)
●(See "COVID-19: General approach to infection prevention in the health care setting".)
●(See "COVID-19: Clinical features".)
●(See "COVID-19: Diagnosis".)
●(See "COVID-19: Outpatient evaluation and management of acute illness in adults".)
●(See "COVID-19: Management in hospitalized adults".)
See specific topic reviews for details on complications of COVID-19 and issues related to COVID-19 in other patient populations.
ASSESSMENT OF SEVERITY — We use the definitions of severity provided in the multicenter interim guidance on the use of antivirals for children with COVID-19 [6]:
●Mild or moderate disease – No new or increased supplemental oxygen requirement
●Severe disease – New requirement for supplemental oxygen or increased requirement from baseline without new or increased need for ventilatory support (noninvasive or invasive)
●Critical disease – New or increased need for noninvasive or invasive mechanical ventilation, sepsis, multiorgan failure, or rapidly worsening clinical trajectory
GENERAL MANAGEMENT CONSIDERATIONS
Use of NSAIDs — Nonsteroidal anti-inflammatory drugs (NSAIDs) that are used chronically for other conditions may be continued unless there are other reasons for discontinuation (eg, gastrointestinal bleeding, renal injury) [7,8]. Either NSAIDs or acetaminophen may be used for symptomatic treatment of pain or discomfort in children with COVID-19. The management of fever in children with COVID-19 is the same as for fever due to other infections and is discussed separately. (See "Fever in infants and children: Pathophysiology and management", section on 'Management of fever'.)
Initial concerns about potential negative effects of NSAIDs in patients with COVID-19 [9,10] have not been supported by most observational data, which have failed to identify worse COVID-19 outcomes with NSAID use compared with acetaminophen or no antipyretic use [11-16]. In a meta-analysis of 11 observational studies (>683,000 participants), exposure to NSAIDs was not associated with increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severe/critical COVID-19 disease, or all-cause mortality [17].
Management of chronic medications
Asthma medications — Considerations related to the safety of glucocorticoid and nebulized medications for children with asthma are discussed separately. (See "An overview of asthma management", section on 'Advice related to COVID-19 pandemic'.)
ACE inhibitors and angiotensin receptor blockers — Children receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) should continue treatment with these agents if there is no other reason for discontinuation (eg, hypotension, acute kidney injury) [18]. This approach is supported by multiple guideline panels [19-23].
Although there has been speculation that patients with COVID-19 who are receiving ACE inhibitors or ARBs may be at increased risk for adverse outcomes, the hypothesis is not supported by findings from observational studies. (See "COVID-19: Issues related to acute kidney injury, glomerular disease, and hypertension", section on 'Renin angiotensin system inhibitors'.)
Immunosuppressive therapy — For children receiving immunosuppressive therapy, we discuss the benefits and risks of reducing immunosuppressive therapy with the prescribing specialist (eg, oncologist, transplant clinician, rheumatologist) [24]. Although the relationship between immune compromise and severe COVID-19 disease has not been well established in children [25,26], management of viral infections in immunocompromised hosts typically includes reduction of baseline immunosuppression, if reduction is possible [27,28]. Information about adjusting immunosuppressive therapy for specific conditions is presented separately. (See "COVID-19: Issues related to solid organ transplantation", section on 'Adjusting immunosuppression' and "COVID-19: Issues related to gastrointestinal disease in adults", section on 'Adjusting IBD medications'.)
Management of multisystem inflammatory syndrome — The management of multisystem inflammatory syndrome in children is discussed separately. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) management and outcome", section on 'Management'.)
Management of possible coinfection with influenza — Recommendations for antiviral therapy for influenza infection in children are unchanged during the COVID-19 pandemic [7]. If indicated, antiviral therapy for influenza can be initiated while awaiting laboratory results. If initiated, antiviral therapy can be discontinued when influenza has been excluded through molecular testing. Antiviral therapy and laboratory testing for influenza are discussed separately. (See "Seasonal influenza in children: Management", section on 'Antiviral therapy' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Diagnosis'.)
MANAGEMENT OF HOSPITALIZED CHILDREN — Children with COVID-19 and severe or critical lower respiratory tract disease generally require hospital admission. Children with nonsevere COVID-19 may require hospital admission if they are at risk for severe disease due to underlying conditions (eg, immune compromise) or are febrile infants younger than 30 days.
Supportive care for all patients — Supportive care should be provided for all pediatric patients with COVID-19 as recommended by various national committees [6,7,29]. Supportive care is the mainstay of therapy for patients with severe or critical COVID-19 [30]. Most children with COVID-19 improve with supportive care, even those with severe disease [6]. (See "COVID-19: Clinical manifestations and diagnosis in children", section on 'Society guideline links'.)
Routine supportive care measures include:
●Provision of respiratory support, including supplemental oxygen and ventilatory support (noninvasive or invasive); respiratory status may change suddenly after approximately one week of symptoms [31]. (See "Initial assessment and stabilization of children with respiratory or circulatory compromise" and "Emergency endotracheal intubation in children".)
●Provision of fluid and electrolyte support. (See "Fluid and electrolyte therapy in newborns" and "Clinical assessment and diagnosis of hypovolemia (dehydration) in children" and "Treatment of hypovolemia (dehydration) in children".)
●Provision of empiric antibiotics as indicated for community-acquired or health care-associated pneumonia; continuation of empiric antibiotics should be determined by cultures and other microbial tests and clinical condition. Bacterial coinfections appear to be infrequent [32-35]. (See "Pneumonia in children: Inpatient treatment".)
●Monitoring for cytokine release syndrome by monitoring blood pressure for hypotension, oxygen saturation for worsening hypoxemia, and biomarkers.
We obtain baseline C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), and interleukin-6 (IL-6).
We monitor CRP, D-dimer, ferritin, and LDH two or three times per week or if there is concern for worsening disease. IL-6 is performed offsite; we repeat it twice per week if it is elevated at baseline or if there is concern for worsening disease.
●Provision of thromboprophylaxis – Interventions to reduce the risk of venous thromboembolism (VTE) may be warranted for children hospitalized with COVID-19 [36].
For hospitalized children without multisystem inflammatory syndrome in children (MIS-C), we make decisions about pharmacologic VTE prophylaxis on a case-by-case basis, considering other VTE risk factors (table 1) and the child's risk of bleeding. Nonpharmacologic strategies for VTE prophylaxis (eg, intermittent pneumatic compression devices [size permitting] and early mobilization) are encouraged. The pharmacologic approach to VTE prophylaxis in hospitalized children is discussed separately. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Approach to VTE prophylaxis'.)
The risk of thrombotic complications in children with COVID-19 has not been well defined. In two multicenter cohort studies (one from the United States, the other from Spain, each including >400 patients), between 1 and 2 percent of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; excluding children with MIS-C) had thrombotic complications (eg, deep vein thrombosis of the upper or lower extremity, pulmonary embolism, intracardiac thrombosis, cerebral sinovenous thrombosis) [37,38]. Most of the patients with thrombotic complications were ≥12 years of age; many had risk factors for thrombosis, and some received thromboprophylaxis before developing thrombosis. Underlying risk factors for thrombosis included cancer, obesity, critical illness, and central venous catheter. The usefulness of D-dimer >5 times the upper limit of normal as a predictor of thrombosis was inconsistent.
The risk of VTE in children with MIS-C and VTE prophylaxis for children with MIS-C is discussed separately. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) management and outcome", section on 'Antithrombotic therapy'.)
SARS-CoV-2 antiviral therapy for select patients — Given the lack of data from controlled trials supporting the efficacy of antiviral agents for the treatment of COVID-19 in children [39], we agree with recommendations from the multicenter interim guidance on the use of antiviral agents for children with COVID-19 and other experts that antiviral therapy should be considered on a case-by-case basis and preferably occur in the context of a clinical trial, if a clinical trial is available [6,40]. Information about ongoing clinical trials is available from ClinicalTrials.gov.
Antiviral therapy for COVID-19 should be reserved for children with documented SARS-CoV-2 infection if testing is available [6].
●Potential indications – Decisions to use antiviral therapy should be individualized according to disease severity, clinical trajectory, existing evidence of effectiveness, and underlying conditions that may increase the risk for progression. Studies of the effectiveness and safety of antiviral therapy have predominantly been performed in adults with severe lower respiratory tract disease [41-43]; these studies are discussed in detail separately. (See "COVID-19: Management in hospitalized adults", section on 'Specific treatments'.)
Despite the unproven benefits, we suggest antiviral therapy for children with documented severe or critical COVID-19. Antiviral therapy also may be warranted for children with mild or moderate disease and an underlying condition that increases or may increase the risk of severe disease (eg, medical complexity, congenital heart disease, among others). (See "COVID-19: Clinical manifestations and diagnosis in children", section on 'Risk factors for severe disease'.)
●Choice of agent/regimen
•Remdesivir – Remdesivir is a prodrug of a nucleotide analog that inhibits RNA-dependent RNA polymerase and has activity against coronaviruses [44-47].
When a decision is made to use antiviral therapy in a child who cannot be enrolled in a clinical trial, we suggest remdesivir rather than other antiviral agents, in agreement with the multicenter panel [6]. Although data regarding the benefits of remdesivir for children with COVID-19 are lacking, it is preferred to other antiviral agents because data from randomized and observational studies in adult patients suggest that it may reduce time to recovery (particularly in patients who are not critically ill) and improve survival; it appears to be well tolerated [6,48-55]. Studies of remdesivir in adult patients with COVID-19 are discussed separately. (See "COVID-19: Management in hospitalized adults", section on 'Remdesivir'.)
When the supply of remdesivir is limited, it should be prioritized for patients with severe rather than critical disease (as defined above); the benefits for those with critical disease are uncertain [7]. (See 'Assessment of severity' above.)
The optimal role of remdesivir in patients with COVID-19 remains uncertain, and some experts (including the World Health Organization [WHO]) suggest not using it in hospitalized patients [56-62]. In the United States, remdesivir has been approved by the US Food and Drug Administration (FDA) for the treatment of COVID-19 requiring hospitalization in adults and children ≥12 years of age who weigh ≥40 kg [63]; it remains available for other hospitalized children with suspected or laboratory-confirmed COVID-19 who weigh ≥3.5 kg through emergency use authorization (EUA) [64,65].
Remdesivir is dosed according to weight as follows:
-≥3.5 to <40 kg – 5 mg/kg intravenous (IV) loading dose on day 1, followed by 2.5 mg/kg IV every 24 hours
-≥40 kg – 200 mg IV loading dose on day 1, followed by 100 mg IV every 24 hours
The usual duration of therapy is up to 5 days for children with severe disease; for children with critical disease who are not improving after 5 days, the duration may be extended to up to 10 days [6,66].
Reported adverse effects of remdesivir include nausea, vomiting, and transaminase elevations. In a review of compassionate use of remdesivir in 77 children hospitalized with severe SARS-CoV-2 infection, 33 percent had adverse events and 16 percent had serious adverse events, most of which were related to COVID-19 or underlying conditions (eg, hypoxia, acute respiratory failure, recurrence of acute lymphocytic leukemia) [67]. The only adverse events to occur in more than one patient were elevation of serum aminotransferases (in nine) and anemia (in two). Cases of bradycardia attributable to remdesivir have also been reported [68-71].
•Baricitinib – Although the FDA has issued an EUA for baricitinib in patients ≥2 years of age who are hospitalized with COVID-19 and require oxygen or ventilatory support, or extracorporeal membrane oxygenation [72], there is limited information about the benefits and risks of baricitinib in children with COVID-19 [7]. It should ideally be used in the context of a clinical trial.
Baricitinib is a Janus kinase inhibitor used for the treatment of rheumatoid arthritis. In addition to its immunomodulatory effects, it is thought to have antiviral effects through interference with viral entry. Baricitinib may provide a mortality benefit for select patients, including those already receiving glucocorticoids. In studies in patients ≥18 years of age, baricitinib appeared to reduce mortality and the combination of baricitinib and remdesivir appeared to modestly improve the time to recovery without increased rates of infection, VTE, or other adverse events [72-74]. Studies of baricitinib in adult patients are discussed separately. (See "COVID-19: Management in hospitalized adults", section on 'Baricitinib and JAK inhibitors'.)
•Monoclonal antibody therapy for children younger than two years – In late January 2022, the FDA paused the EUA for combination bamlanivimab-etesevimab in children <2 years of age hospitalized with mild to moderate COVID-19 who are at risk of progression to severe disease [75,76]. The EUA was paused due to the widespread high frequency of circulation of the Omicron (B.1.1.529) variant, which is highly unlikely to be susceptible to bamlanivimab-etesevimab (table 2) [77].
•Hydroxychloroquine and chloroquine – We recommend not using hydroxychloroquine or chloroquine for the treatment of COVID-19 in children. It has not been proven effective and is associated with severe adverse reactions [78-82]. Hydroxychloroquine is not licensed for this indication, and its EUA for the treatment of COVID-19 in the United States has been revoked [83,84].
•Lopinavir-ritonavir – We do not recommend routine use of lopinavir-ritonavir given the absence of efficacy and unfavorable pharmacodynamics [29,42,43,56,85]. (See "COVID-19: Management in hospitalized adults", section on 'Others'.)
Individualized adjunctive therapy
Glucocorticoids — We make decisions about the use of glucocorticoids for immune-mediated complications of COVID-19 on a case-by-case basis according to disease severity [86]. Although glucocorticoids have been associated with decreased mortality in adult patients [57,87], trials in children are ongoing and the benefits and risks are uncertain. Pending results of these trials, administration of glucocorticoids ideally should occur in the context of a clinical trial. Information about ongoing clinical trials is available from ClinicalTrials.gov.
For select children with severe or critical COVID-19 who cannot participate in a clinical trial (ie, those who require mechanical ventilation or those who require supplemental oxygen and have risk factors for disease progression), low-dose glucocorticoids may be warranted [86,88]; the duration of therapy is up to 10 days or until discharge, whichever is shorter. Low-dose glucocorticoid regimens include one of the following (dexamethasone is preferred if available) [7,88,89]:
●Dexamethasone 0.15 mg/kg orally, IV, or nasogastrically (NG) once daily (maximum dose 6 mg)
●Prednisolone 1 mg/kg orally or NG once daily (maximum dose 40 mg)
●Methylprednisolone 0.8 mg/kg IV once daily (maximum dose 32 mg)
•For neonates (<1 month of age) – 0.5 mg/kg IV every 12 hours for 7 days followed by 0.5 mg/kg IV once daily for 3 days
•For children ≥1 month – 1.3 mg/kg IV every 8 hours (maximum dose 50 mg; maximum total daily dose 150 mg)
The use of glucocorticoids is supported by randomized trials comparing glucocorticoids with placebo or usual care, predominantly in adult patients with severe or critical COVID-19. In a meta-analysis of seven randomized trials, in a total of 1703 critically ill patients [90-93], glucocorticoids reduced 28-day all-cause mortality (33 versus 41 percent, odds ratio 0.66, 95% CI 0.53-0.82) without increased serious adverse events [87]. The results were similar with dexamethasone or hydrocortisone. Another meta-analysis of randomized trials comparing glucocorticoids with standard care irrespective of disease severity concluded that glucocorticoids probably reduce all-cause mortality at a median of 28 days (24.5 versus 27.5 percent; risk ratio 0.89, 95% CI 0.80-1.00) and may increase ventilator-free days [94]. (See "COVID-19: Management in hospitalized adults", section on 'Dexamethasone and other glucocorticoids'.)
Although the WHO strongly recommends systemic glucocorticoids for patients with severe or critical COVID-19, they acknowledge that the applicability of the recommendation for children is uncertain because children were underrepresented in the clinical trials supporting benefit [88]. (See 'Society guideline links' below.)
Glucocorticoids plus tocilizumab — Tocilizumab is a monoclonal antibody that reduces inflammation by blocking the IL-6 receptor. It is used in the management of several rheumatologic conditions in children and adults (eg, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome).
Although the FDA has issued an EUA for tocilizumab in hospitalized patients ≥2 years of age who are receiving systemic glucocorticoids and require supplemental oxygenation, mechanical ventilation (noninvasive or invasive), or extracorporeal membrane oxygenation [95], there is limited information about the benefits and risks of this therapy in children with COVID-19 [7,56]. It should ideally be used in the context of a clinical trial.
Tocilizumab is dosed according to patient weight [95]:
●<30 kg – 12 mg/kg IV in a single 60-minute infusion
●≥30 kg – 8 mg/kg IV in a single 60-minute infusion (maximum 800 mg per infusion)
Tocilizumab may be repeated once ≥8 hours after the initial infusion if clinical signs or symptoms worsen or do not improve after the first dose.
Tocilizumab should be avoided in individuals with hypersensitivity to tocilizumab, uncontrolled serious infections other than COVID-19, absolute neutrophil count <1000 cells/microL, platelet counts <50,000/microL, alanine aminotransferase >5 times the upper limit of normal, or elevated risk for gastrointestinal perforation [7,95]. Tocilizumab should be used with caution in immunocompromised individuals as very few were included in randomized trials. Administration of live vaccines (eg, measles, mumps, rubella, varicella) should be deferred for at least two weeks after the final infusion of tocilizumab [96]; some experts would wait at least four weeks before administration of live vaccines.
Tocilizumab may reduce progression to mechanical ventilation, duration of hospitality, and mortality in adults with COVID-19, but the findings are inconsistent. Studies describing the use of tocilizumab in adult patients with COVID-19 are discussed separately. (See "COVID-19: Management in hospitalized adults", section on 'IL-6 pathway inhibitors (eg, tocilizumab)'.)
In adult patients with COVID-19, the most commonly reported adverse reactions were constipation, diarrhea, nausea, anxiety, insomnia, hypertension, and superinfection [95,97].
Other adjunctive therapies — We make decisions about the use of other adjunctive therapies for immune-mediated complications of COVID-19 on a case-by-case basis according to disease severity and in consultation with specialty services as indicated (eg, rheumatology, infectious diseases) [86]. The immune response to SARS-CoV-2 is variable and may include marked systemic inflammation and/or immune suppression [98].
We do not routinely use other immune modulators (interferon alfa-2b, interferon-beta 1b, convalescent plasma from recovered COVID-19 patients) in the treatment of children hospitalized with COVID-19, except in the context of a clinical trial [86]. The benefits and risks are uncertain [7,86,99-107]. The use of immune-modifying therapies in children with multisystem inflammatory syndrome and the use of immune-modifying therapies in adults are discussed separately. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) management and outcome", section on 'Immune-modifying therapies' and "COVID-19: Management in hospitalized adults", section on 'COVID-19-specific therapy'.)
Information about ongoing clinical trials is available from ClinicalTrials.gov.
Although there are no available data on the use of vitamin A for the treatment of COVID-19, vitamin A has long been used as an adjunctive therapy in the treatment of measles, and its use has been associated with decreased morbidity and mortality from measles-associated pneumonia [108]. Vitamin A deficiency may be associated with impairment of humoral and cell-mediated immunity, and even mild vitamin A deficiency may lead to increased morbidity from measles and other viral respiratory infections [108]. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention", section on 'Vitamin A'.)
OUTPATIENT MANAGEMENT
Telephone triage — The United States Centers for Disease Control and Prevention (CDC) provides guidance for telephone advice for people ≥2 years of age with possible COVID-19.
Outpatient therapy for select children
Approach — We consider outpatient therapy for children with mild-to-moderate COVID-19 disease who are at high risk for progression to severe disease on a case-by-case basis. Robust evidence associating specific underlying conditions with progression to severe illness in children is limited [6,109].
Potential indications for outpatient therapy in children include lack of vaccination against COVID-19, expected inadequate response to COVID-19 vaccine (eg, due to immunosuppressive disease or immunosuppressive therapies), medical-related technologic dependence not related to COVID-19 (eg, tracheostomy, positive pressure ventilation), having obesity (body mass index ≥95th percentile for age and sex [males: (calculator 1), females: (calculator 2)]), and having multiple underlying conditions [110,111].
When outpatient antiviral therapy is warranted for children with COVID-19, we suggest nirmatrelvir-ritonavir, sotrovimab, or intravenous (IV) remdesivir rather than other therapies. Bebtelovimab is an alternative for children ≥12 years of age who weigh ≥40 kg, and molnupiravir is an alternative for patients ≥18 years of age if nirmatrelvir-ritonavir, sotrovimab, and remdesivir are unavailable or clinically inappropriate. Although there is limited information about the effectiveness of these interventions in children and adolescents, in randomized trials in nonhospitalized adults, they substantially reduced the risk of hospitalization. (See "COVID-19: Outpatient evaluation and management of acute illness in adults", section on 'Treatment with COVID-19-specific therapies'.)
Administration of these agents is discussed below. (See 'Antiviral therapies' below and 'Outpatient monoclonal antibody therapy' below.)
We choose among the suggested therapies on a case-by-case basis, considering the [7,29]:
●Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant (if known) or the prevalence of circulating SARS-CoV-2 variants, which affects susceptibility (table 2).
Given the high frequency of circulation of the Omicron (B.1.1.529) variant throughout the United States, bamlanivimab-etesevimab and casirivimab-imdevimab are no longer authorized for use in the United States (including territories and jurisdictions) [75,76].
In the United States, the regional prevalence of circulating variants is available from the CDC.
●Local availability of therapies; limited supplies may warrant prioritization for those at highest risk of severe disease (table 3) [7,112] (ie, unvaccinated children and children expected to have an inadequate vaccine response).
●Duration of symptoms; all of the available outpatient therapies should be initiated as soon as possible after positive SARS-CoV-2 test and within a specified time from symptom onset:
•Five days for nirmatrelvir-ritonavir and molnupiravir
•Seven days for remdesivir and bebtelovimab
•Ten days for sotrovimab
●Feasibility of administering parenteral medications (eg, remdesivir, monoclonal antibodies)
●Child's age; the therapies are approved or authorized for particular age groups:
•Age <12 years and weight ≥3.5 kg – Remdesivir (through emergency use authorization [EUA])
•Age ≥12 years and weight ≥ 40 kg – Sotrovimab (EUA), bebtelovimab (EUA), nirmatrelvir-ritonavir (EUA), remdesivir (US Food and Drug Administration [FDA] approved)
•Age ≥18 years – Molnupiravir (EUA)
●Comorbidities and potential for drug-drug interactions (particularly with nirmatrelvir-ritonavir)
Antiviral therapies
●Nirmatrelvir-ritonavir — Nirmatrelvir-ritonavir is an oral protease inhibitor that prevents viral replication. It is expected to retain activity against Omicron, but data are limited [7].
The FDA issued an EUA for nirmatrelvir-ritonavir for the treatment of mild-to-moderate COVID-19 disease in adults and children who are ≥12 years of age and weigh ≥40 kg with documented SARS-CoV-2 infection who are at high risk for progression to severe disease (table 4) [113]. In unpublished randomized trials in adult outpatients, nirmatrelvir-ritonavir reduced the risk of hospitalization or death. Data in children are limited. (See "COVID-19: Outpatient evaluation and management of acute illness in adults", section on 'Nirmatrelvir-ritonavir'.)
•Timing and dose – Nirmatrelvir-ritonavir should be initiated as soon as possible following COVID-19 diagnosis and within five days of symptom onset.
The dose for children ≥12 years of age who weigh ≥40 kg is 300 mg nirmatrelvir (two 150 mg tablets) with one 100 mg ritonavir tablet taken together orally twice daily for five days [113]. For patients with moderately reduced kidney function (estimated glomerular filtration rate [eGFR] 30 to 59 mL/min), the dose is one 150 mg nirmatrelvir tablet and one 100 mg ritonavir tablet taken together twice daily for five days. Nirmatrelvir-ritonavir is not recommended for patients with eGFR <30 mL/min or for patients with severe hepatic impairment (Child-Pugh class C) (table 5).
•Contraindications and precautions – Nirmatrelvir-ritonavir is a CYP3A inhibitor, and coadministration is contraindicated with many drugs that are highly dependent upon CYP3A for clearance and in which an elevated level may be dangerous [113]. Coadministration is also contraindicated with potent CYP3A inducers, which may reduce levels of nirmatrelvir and/or ritonavir and result in loss of efficacy or resistance. Specific interactions of nirmatrelvir-ritonavir with other medications may be determined using the Lexicomp drug interactions tool (Lexi-Interact) included in UpToDate.
The decision to use nirmatrelvir-ritonavir in patients with uncontrolled/untreated HIV should factor in the potential risk of causing HIV protease inhibitor resistance [113].
●Remdesivir — IV remdesivir is commercially available and another option for nonhospitalized children with a positive test for SARS-CoV-2 who have symptomatic mild-to-moderate COVID-19 and are at risk for progression to severe disease [7]. It is approved for children ≥12 years who weigh ≥40 kg. For other nonhospitalized children who weigh ≥3.5 kg, IV remdesivir is available through EUA [65]. In a randomized trial in nonhospitalized adults with at least one risk factor for disease progression, remdesivir reduced the risk of hospitalization [114].
Remdesivir should be initiated as soon as possible and within seven days of symptom onset. It is dosed according to weight as follows:
•≥3.5 to <40 kg – 5 mg/kg IV day 1, followed by 2.5 mg/kg IV on days 2 and 3
•≥40 kg – 200 mg IV on day 1, followed by 100 mg IV on days 2 and 3
Given the three-day regimen, remdesivir may be most feasible for children and adolescents residing in skilled nursing facilities.
●Molnupiravir — Molnupiravir is a nucleoside analogue that inhibits SARS-CoV-2 replication. It is available through EUA for the treatment of mild-to-moderate COVID-19 in nonpregnant individuals ≥18 years of age who are at high risk for progression to severe disease and for whom other authorized treatments are not accessible or clinically appropriate [115]. It is discussed separately. (See "COVID-19: Outpatient evaluation and management of acute illness in adults", section on 'Molnupiravir'.)
Outpatient monoclonal antibody therapy
●Potential indications – Monoclonal antibody therapy is available through EUA for nonhospitalized patients who have mild to moderate illness (ie, no new or increased supplemental oxygen requirement) and are at high risk of progression to severe disease, including hospitalization or death (table 6) [56,77,116-118].
We agree with the American Academy of Pediatrics and multidisciplinary panel that decisions about the use of monoclonal antibodies in children should be made on a case-by-case basis [110,111]. If employed, monoclonal antibody therapy ideally should occur in the context of a clinical trial and should consider risk factors supported by evidence from studies in children (eg, immunosuppressive disease or therapies, medical-related technologic dependence not related to COVID-19, obesity, multiple underlying conditions) [7,86].
In a meta-analysis of five randomized trials comparing monoclonal antibody therapy with placebo in nonhospitalized adults and adolescents [119-123], monoclonal antibody therapy reduced the rate of hospitalization or emergency department visits (1.7 versus 6.5 percent, odds ratio [OR] 0.26, 95% CI 0.19-0.36), hospitalization (OR 0.24, 95% CI 0.17-0.34), and mortality (OR 0.16, 95% CI 0.05-0.58) [124]. However, limited numbers of children were included, proven risk factors that reliably predict poor outcomes in children are lacking, and the benefits and risks in children remain uncertain [110,111,125,126].
●Use with SARS-CoV-2 variants– SARS-CoV-2 variants with mutations that affect the spike protein may have reduced susceptibility to available monoclonal antibody therapies (table 2) [75].
Information regarding the susceptibility of specific variants is available in the FDA fact sheets for sotrovimab, bebtelovimab, bamlanivimab-etesevimab, and casirivimab-imdevimab [77,116-118]. Information about the relative proportions of SARS-CoV-2 variants circulating in local areas is available from the CDC and state and local health authorities [127]. Given the increased prevalence of resistant variants, the FDA revoked the emergency use authorization for bamlanivimab monotherapy in April 2021 [128] and paused the authorization for bamlanivimab-etesevimab and casirivimab-imdevimab in late January 2022 [75,76]. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Variants of concern'.)
●Available monoclonal antibodies
•Sotrovimab – For high-risk children with a positive direct SARS-CoV-2 test who do not have access to a clinical trial, sotrovimab (an antispike-neutralizing monoclonal antibody) is available under EUA from the FDA for use in children ≥12 years of age who weigh ≥40 kg [117]. Sotrovimab is active against the Delta and Omicron variants. It is preferred to bebtelovimab if it is available.
The regimen for sotrovimab is 500 mg IV as a single IV infusion. It should be administered as soon as possible after positive SARS-CoV-2 test and within 10 days of symptom onset [117].
EUA for sotrovimab was supported by interim analysis of a randomized trial that included 583 patients in which sotrovimab reduced hospitalization or death at 29 days (1 versus 7 percent) compared with placebo [122] and reduced viral load [117].
•Bebtelovimab – For high-risk children with a positive direct SARS-CoV-2 test who do not have access to a clinical trial, bebtelovimab (an antispike-neutralizing monoclonal antibody) is available under EUA from the FDA for use in children ≥12 years of age who weigh ≥40 kg and for whom other approved or authorized COVID-19 therapies are not accessible or clinically appropriate [118]. Bebtelovimab is active against the Delta and Omicron variants.
The regimen for bebtelovimab is 175 mg IV as a single IV infusion. It should be administered as soon as possible after positive SARS-CoV-2 test and within seven days of symptom onset [118].
EUA for bebtelovimab was supported by several treatment arms of a Phase 2 randomized trial in patients without risk factors for severe COVID-19 in which bebtelovimab (with or without other monoclonal antibodies) reduced duration of symptoms (6 to 7 versus 8 days) and viral load on day 5 compared with placebo [118]. In a separate part of the trial in high-risk patients, 29-day rates of hospitalization and death were similar among high-risk patients assigned to bebtelovimab alone and bebtelovimab with other monoclonal antibodies (3 to 4 percent), and generally were lower than the rates among high-risk patients assigned to placebo in previous trials of monoclonal antibody therapy during in which the circulating variants and risk factors varied.
●Other monoclonal antibodies – EUA for bamlanivimab-etesevimab and casirivimab-imdevimab was paused in late January 2022 given the high frequency of circulation of the Omicron variant throughout the United States [75,76].
●Adverse effects – Reported adverse effects of monoclonal antibody therapy for COVID-19 include fever, chills, dizziness, dyspnea, urticaria, pruritus, flushing, nausea, and vomiting [77,116-118].
●Education
•Isolation – Children who are treated with monoclonal antibodies should continue to self-isolate and follow infection control measures as recommended below. (See 'Prevention of transmission' below.)
●Vaccination – Persons who receive monoclonal antibody therapy for SARS-CoV-2 infection can be vaccinated against COVID-19 at any time. COVID-19 vaccination does not need to be delayed after receipt of monoclonal antibodies [129].
How should children be managed at home? — Children with documented or suspected COVID-19 and mild symptoms (eg, fever, cough, pharyngitis, other respiratory symptoms) generally should be managed at home unless they have a chronic condition that increases their risk of severe disease.
Management is focused on prevention of transmission to others (ie, isolation), monitoring for clinical deterioration, and supportive care. The CDC and World Health Organization (WHO) provide additional guidance on what to do when someone is sick [130,131]. (See 'Prevention of transmission' below.)
The clinical course for symptomatic children and adolescents may be prolonged, but specific data are lacking. Although few studies have evaluated the clinical course of COVID-19 in children [132], persistent physical symptoms (eg, fatigue, joint pain, cough) are common in adults. (See "COVID-19: Evaluation and management of adults following acute viral illness", section on 'Persistent symptoms'.)
●Monitoring for clinical deterioration – Caregivers of children who are managed at home should be counseled about symptoms of clinical deterioration, which may occur suddenly after approximately one week of symptoms and should prompt urgent re-evaluation [31]. Among 121 SARS-CoV-2-associated deaths in children and adolescents reported to the CDC, 33 percent occurred at home or in the emergency department, suggesting that delayed or deferred medical care may have played a role [133].
Manifestations of clinical deterioration include [130,131,134,135]:
•Severe respiratory distress, difficulty breathing (for infants: grunting, central cyanosis, inability to breastfeed)
•Chest pain or pressure
•Blue lips or face
•Findings associated with shock (eg, cold, clammy, mottled skin; new confusion; difficulty arousing; substantially reduced urine output)
•Inability to drink or keep down any liquids
●Symptomatic and supportive care – Symptomatic care for COVID-19 in the outpatient setting is similar to that for other upper respiratory or gastrointestinal clinical syndromes:
•Upper respiratory tract infection (see "The common cold in children: Management and prevention", section on 'Symptomatic therapy')
•Pharyngitis (see "Acute pharyngitis in children and adolescents: Symptomatic treatment", section on 'Symptomatic treatment')
•Acute gastroenteritis (see "Acute viral gastroenteritis in children in resource-rich countries: Management and prevention", section on 'Management')
The management of fever in children, including indications for treatment, are discussed separately. (See "Fever in infants and children: Pathophysiology and management", section on 'Management of fever'.)
When can home isolation be discontinued? — The optimal duration of home isolation is uncertain. How long a person remains infectious is uncertain. The duration of viral shedding is variable; there appears to be a wide range, which may depend on severity of illness, underlying conditions, and treatment [136]. Among 110 children at Wuhan Children's Hospital, the median duration of viral shedding was 15 days from onset of illness (interquartile range 11 to 20 days); the duration was longer for symptomatic than asymptomatic children (17 versus 11 days) [137]. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Viral shedding and period of infectiousness'.)
The CDC has issued recommendations for ending isolation and precautions for patients with symptoms, patients without symptoms, and patients who are moderately or severely immunocompromised [138]. The WHO has also issued recommendations on discontinuation of isolation for patients with and without symptoms [139].
Adequate vitamin D intake — Adequate intake of vitamin D is necessary for bone health. Vitamin D supplementation may be necessary to meet the recommended intake (table 7), particularly for children with limited exposure to sunlight (eg, those remaining inside while self-isolating). However, the role of vitamin D in the treatment and prevention of COVID-19 is uncertain, and doses exceeding the upper level intake are not recommended [7,140-144]. (See "Vitamin D and extraskeletal health", section on 'COVID-19' and "Overview of vitamin D".)
Whether vitamin D deficiency increases the risk of SARS-CoV-2 infection in children is uncertain [145]. The association may be confounded by other risk factors for both vitamin D deficiency and SARS-CoV-2 infection (eg, obesity) [143,146]. Vitamin D deficiency in children, including indications for screening (which are unchanged by the COVID-19 pandemic), is discussed separately. (See "Vitamin D insufficiency and deficiency in children and adolescents".)
Avoidance of unproven interventions — Neither azithromycin nor hydroxychloroquine/chloroquine have been proven effective in improving symptoms or preventing progression in patients with COVID-19. We recommend not using them in the management of SARS-CoV-2 in children [7,29,110,147-149].
Investigational agents, including fluvoxamine and ivermectin, should be used only in the context of a clinical trial [7,29,56]. Misuse of forms of these agents not intended for humans (eg, veterinary ivermectin) may lead to severe toxicity, including death [150-152].
Although preliminary studies of fluvoxamine in adult patients suggest benefits in reducing hospitalization, death, and/or disease progression, additional data are needed before it can be recommended for children outside of a clinical trial. (See "COVID-19: Outpatient evaluation and management of acute illness in adults", section on 'Therapies of limited or uncertain benefit'.)
FOLLOW-UP — The type (eg, telehealth versus in-person visit with primary care provider or specialist), timing, and content of follow-up for children and adolescents recovering from acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is individualized according to underlying comorbidities, severity of illness, persistence of symptoms, and complications. We follow the guidance provided by the American Academy of Pediatrics (AAP) [153].
●Children without multisystem inflammatory syndrome in children (MIS-C) – Children with >4 days of symptoms (eg, fever, chills, myalgia, lethargy) and children who required hospitalization may require phone or video follow-up during isolation to ensure continued recovery [153]. After the isolation period is over and before return to physical activity, they should have an in-person visit. Children with asymptomatic or mild disease (<4 days of symptoms) and resolution of symptoms can have follow-up by video, phone, or in person (after the isolation period is over) before return to physical activity.
The follow-up visit should address:
•Ongoing and newly developed symptoms, including cardiorespiratory symptoms, loss of smell or taste (may manifest in feeding changes in young children), neurodevelopmental symptoms (eg, motor, cognitive, language impairment; inattention; memory problems), fatigue, headache, and mental health sequelae [153]. In addition, children with a history of SARS-CoV-2 infection should be screened for diabetes symptoms (eg, increased thirst, increased hunger, frequent urination, weight loss, fatigue, abdominal pain, nausea, vomiting); SARS-CoV-2 infection has been associated with increased incidence of diabetes mellitus >30 days after infection [154-156].
Children with ongoing symptoms and worrisome signs should be evaluated as clinically indicated (eg, for myocarditis or MIS-C, intracranial pathology in children with headache and worrisome features (table 8)).
Otherwise, we minimize diagnostic testing and provide supportive care focused on improving function (eg, by setting achievable goals) for the first 12 weeks of recovery [153,157]. Although persistent symptoms may be related to SARS-CoV-2 infection, they also may be related to the conditions of the pandemic (eg, social isolation, death of a family member, trauma of hospitalization, decreased physical activity) [158-161].
The Centers for Disease Control and Prevention, AAP, and World Health Organization (WHO) use the umbrella term "post-COVID-19 condition" for the broad range of physical and mental health symptoms present ≥4 weeks after SARS-CoV-2 infection (of any severity) [153,157,162]. The WHO provides a consensus clinical case definition that requires symptoms that last ≥2 months, cannot be explained by an alternative diagnosis, and generally affect everyday function [162]. Additional testing or referral to a multidisciplinary post-COVID-19 clinic may be warranted for children whose symptoms persist for >12 weeks [153].
•Behavioral and mental health surveillance [163].
•Guidance for return to activity (eg, school, sports, employment), including provision of support as indicated (eg, gradual return to school).
-Before returning to physical activity (eg, organized sports training, practice, or competition; physical education class within school; recreational sports), children should be evaluated by their clinician for cardiac symptoms (eg, chest pain, palpitations, syncope, shortness of breath out of proportion to respiratory tract illness) because of the possibility cardiac complications of SARS-CoV-2 [164]. Return to play following COVID-19 is discussed separately. (See "COVID-19: Return to play or strenuous activity following infection".)
•COVID-19 immunization (if eligible) and catch-up of routine immunizations (if necessary). (See "COVID-19: Vaccines" and "Standard immunizations for children and adolescents: Overview", section on 'Catch-up schedule'.)
•Reinforcement of strategies to prevent infection. (See 'Prevention of transmission' below.)
•Education about symptoms that should prompt re-evaluation. (See 'How should children be managed at home?' above.)
•Healthy habits – Adequate nighttime sleep, maintaining a consistent daily schedule, adequate hydration and nutrition, and avoidance of alcohol and drugs.
Testing for SARS-CoV-2 after recovery is not recommended unless the child or adolescent is symptomatic or has been exposed to someone recently diagnosed with SARS-CoV-2 infection. A negative SARS-CoV-2 test is not necessary to discontinue isolation. (See 'When can home isolation be discontinued?' above.)
●Children with MIS-C – Follow-up of children with MIS-C is discussed separately. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) management and outcome", section on 'Follow-up'.)
PREVENTION OF TRANSMISSION
From infected mother to newborn — Prevention of transmission from infected mother to newborn after delivery is discussed separately. (See "COVID-19: Intrapartum and postpartum issues", section on 'Postpartum care of infected patients'.)
From children with documented or suspected COVID-19
During cardiopulmonary resuscitation — Modifications to algorithms for pediatric basic and advanced life support to prevent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are discussed separately. (See "Pediatric basic life support (BLS) for health care providers", section on 'COVID-19 patients (suspected or confirmed)' and "Pediatric advanced life support (PALS)", section on 'COVID-19 patients (suspected or confirmed)'.)
Hygiene and social distancing — Prevention of transmission focuses on hygiene and social distancing. This includes [130,131,165]:
●Having friends or family members bring necessary items to the home (to be retrieved outside).
●Having the child (and other sick household members) wear a mask if leaving the home cannot be avoided. At the time of discharge, if supplies allow, providing patients with a pair of gloves and several masks may help to prevent transmission to household contacts. In addition, for patients without access to private transportation, arranging medical transportation, if possible, is preferable to the use of public transportation or ride-sharing services to minimize exposure to the public.
●As much as possible, keeping ill household members ≥6 feet away from other people, especially household members who are ≥65 years of age or have serious medical conditions.
If such separation is not possible, have the ill household members wear a face mask when they are in the same room or vehicle as other people.
●Keeping ill household members separated from pets in the household.
●Having household members who have fever or cough sleep in separate rooms and use separate bathrooms.
●Avoiding sharing items (eg, pillows, blankets, utensils, cups).
Additional information about how to care for people with documented, suspected, or possible COVID-19 at home is available from the United States Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) [130,131].
Disinfection — Disinfection of frequently touched surfaces is also important, as discussed separately. (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection", section on 'Environmental disinfection'.)
Caregivers should be counseled to avoid the following practices [166]:
●Using bleach on food products
●Applying household cleaning and disinfectant products to skin
●Ingesting or inhaling household cleaning and disinfectant products
From asymptomatic frontline workers to household members — Specific guidance for prevention of asymptomatic transmission from asymptomatic frontline/essential workers with potential unrecognized exposure to SARS-CoV-2 to household members is lacking. In addition to COVID-19 vaccination, adherence to prevention strategies during work (eg, use of personal protective equipment, handwashing) is recommended. The CDC provides additional recommendations to prevent transmission of COVID-19 outside of work, including physical distancing and other personal prevention strategies [167]. The CDC recommends that individuals who live in areas with a high COVID-19 community level wear a mask indoors in public [168-170]. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Prevention'.)
In addition, health care and other frontline workers may choose to implement additional measures after work (eg, changing out of work clothes and shoes and/or showering before contact with household members), although it is uncertain whether these practices lower the risk of transmission. Physical distancing, use of disposable masks or cloth face coverings, and/or improving ventilation in the home also may be warranted, particularly if household members are at increased risk for severe infection [171,172]. (See "COVID-19: Clinical manifestations and diagnosis in children", section on 'Risk factors for severe disease'.)
For asymptomatic children without known exposure
Should routine health supervision appointments be rescheduled? — During the COVID-19 pandemic, the benefits of well-visits should be balanced with the risk of exposure to COVID-19 and other communicable illnesses, within the context of patient population and office environment [173-175]. When clinicians or practices are unable to provide well-child visits to all of the patients in their practice, the CDC and American Academy of Pediatrics (AAP) encourage prioritization of newborn care and vaccination of children through 24 months of age [174,176]. (See 'Disruption of immunization' below.)
Scheduling home visits, telemedicine, office space, and/or office locations can be used to keep well children and children who are ill or possibly ill separated (eg, scheduling well-visits in the morning and sick visits in the afternoon, seeing children for sick visits in a different part of the clinic, designated examination rooms, or at a different office site [or practice] than children for well-visits) [173,177-179].
The AAP provides information and resources about telemedicine, including information about state-by-state payer policies.
Use of cloth face coverings or disposable masks — The CDC recommends that individuals ≥2 years of age wear a tightly fitted disposable mask or cloth face covering (eg, homemade mask) if they have symptoms, have tested positive for SARS-CoV-2, have been exposed to someone with COVID-19, or are using public transportation other than vans or buses operated by school systems (public or private) [180,181].
In addition, although local regulations should be followed, the CDC recommends that individuals ≥2 years of age wear a tightly fitted disposable mask or cloth face covering (eg, homemade mask) when they are in indoor public settings in areas where the COVID-19 community level is high [169,170,182]. Masks that are most protective, fit well, and will be worn consistently are preferred; the preferred mask type may vary from person to person [183].(See "COVID-19: Epidemiology, virology, and prevention", section on 'Variants of concern'.)
Cloth face coverings or masks are not recommended for children <2 years of age because of concerns about suffocation [184]. The AAP provides additional information about cloth face coverings and masks for children, including tips for increasing proper wearing and use and guidance for indoor and outdoor mask use in unvaccinated children. Recommendations from the CDC and AAP regarding cloth face coverings and masks for children and adolescents in the school setting are provided below. (See 'In-person school and child care' below.)
The WHO and United Nations Children's Fund (UNICEF) advise against masks for children age 5 years and younger, and suggest a risk-based approach for children age 6 through 11 years that considers the level of transmission in community, feasibility, discomfort, concerns about social interaction and communication, and availability of adult supervision and other ways of preventing transmission [185]. For children ≥12 years of age, the WHO and UNICEF recommend the same approach as for adults (ie, mask/cloth face covering as part of a comprehensive approach to reducing SARS-CoV-2 transmission in settings where there is widespread transmission and social distancing is difficult [eg, in public settings, in congregate living settings, on public transportation]). (See "COVID-19: Epidemiology, virology, and prevention", section on 'Wearing masks in the community'.)
Should play dates and playgrounds be avoided? — When gathering with children from other households, caregivers should consider whether family members or close contacts are at increased risk for severe COVID-19 disease (eg, immunocompromised or with certain underlying conditions) and the COVID-19 vaccination status of individual family members [186].
Steps caregivers can take to protect their children include [167]:
●Getting eligible children vaccinated against COVID-19 (see "COVID-19: Vaccines", section on 'Children')
●Gathering outside when possible
●Keeping children ≥6 feet from people from other households when they are indoors in public
●Avoiding poorly ventilated spaces and crowds
●Having children ≥2 years of age wear a tightly fitted disposable mask or cloth face covering indoors in public spaces in areas where the COVID-19 community level is high (see 'Use of cloth face coverings or disposable masks' above)
The CDC provides information about how to safely remain physically active at parks and recreational facilities during the COVID-19 pandemic.
For asymptomatic children with potential exposure — The management of asymptomatic children with potential exposure to COVID-19, including self-quarantine and monitoring for symptoms, is discussed separately. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Post-exposure management'.)
Hand sanitizer safety — Although washing hands with soap and water is preferred whenever possible, alcohol-based hand sanitizer is safe for use in children when the sanitizer is used according to the information on the Drug Facts label; there is no cause for concern if children eat or lick their hands after the hand sanitizer has fully dried [187].
Counseling regarding safe use of alcohol-based hand sanitizer includes [187-189]:
●Use hand sanitizer in a well-ventilated area; inhalation of alcohol vapors may be associated with adverse effects (eg, dizziness, nausea, headache) [188]
●Avoid homemade hand sanitizer, which may be ineffective or cause skin burns
●Keep hand sanitizers out of the reach and sight of children
●Supervise the use of hand sanitizer in children younger than six years to avoid ingestion and/or eye exposure from touching the eyes or splashing
•Systemic toxicity – Even a small amount of liquid hand sanitizer can cause alcohol poisoning in children (including hypoglycemia) [190]. (See "Ethanol intoxication in children: Epidemiology, estimation of toxicity, and toxic effects" and "Ethanol intoxication in children: Clinical features, evaluation, and management".)
Hand sanitizers made with isopropyl alcohol (isopropanol) may be more toxic than those that contain ethanol (ethyl alcohol) [191]. Hand sanitizers that contain methanol (methyl alcohol) or methylated spirits should be avoided; ingestion of methanol can be life threatening [191-193]. The US Food and Drug Administration (FDA) has noted an increase in hand sanitizer products that are labeled to contain ethanol but have tested positive for contamination with methanol or 1-propanol. The FDA provides a list of these products and other products that contain potentially harmful ingredients on its website. In addition, the FDA has placed all alcohol-based hand sanitizers from Mexico on import alert because of frequent contamination with toxic ingredients, including methanol and 1-propanol [194]. (See "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis" and "Methanol and ethylene glycol poisoning: Management".)
•Eye injury – Eye exposure may result in severe injury [189,195-197]. In the event of eye exposure, rinse the eyes immediately with gently running water (eg, from a sink tap, water bottle, emergency shower) for at least 15 to 20 minutes. Patients who develop symptoms after rinsing (eg, redness, pain, irritation, visual impairment, photophobia) should seek urgent eye examination [189].
PRE-EXPOSURE PROPHYLAXIS
SARS-CoV-2 immunization — Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization is the optimal method of pre-exposure prophylaxis for eligible individuals. The Centers for Disease Control and Prevention provide a vaccination toolkit for pediatric health care professionals.
SARS-CoV-2 immunization is discussed separately. (See "COVID-19: Vaccines" and "COVID-19: Allergic reactions to SARS-CoV-2 vaccines".)
Pre-exposure prophylaxis with monoclonal antibodies — In the United States, the Food and Drug Administration has granted emergency use authorization for copackaged tixagevimab-cilgavimab for pre-exposure prophylaxis for individuals ≥12 years (weighing ≥40 kg) who may not have an adequate response to COVID-19 vaccination or who cannot receive a full series of a COVID-19 vaccine because of a severe adverse reaction to the vaccines or their components. Tixagevimab-cilgavimab is active against the Omicron (B.1.1.529) variant, but activity is reduced by 12- to 30-fold compared with the ancestral virus [198,199]. Pre-exposure prophylaxis is discussed separately. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Pre-exposure prophylaxis'.)
POSTEXPOSURE PROPHYLAXIS
Monoclonal antibodies — No monoclonal antibodies are approved or authorized for postexposure prophylaxis in the United States. In late January 2022, the FDA paused the emergency use authorization (EUA) for combination bamlanivimab-etesevimab and combination casirivimab-imdevimab due to the widespread high frequency of circulation of the Omicron variant, which is highly unlikely to be susceptible to bamlanivimab-etesevimab or casirivimab-imdevimab (table 2) [75,77,116]. Neither sotrovimab nor bebtelovimab is authorized for postexposure prophylaxis [117,200].
Other agents — We avoid postexposure prophylaxis with hydroxychloroquine. In a meta-analysis of three randomized trials [201-203], rates of symptomatic infection (approximately 9 percent), hospitalization (<1 percent), and death (<1 percent) were similar in hydroxychloroquine and placebo groups [29].
Other agents for prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being evaluated in clinical trials, but none has been proven effective in children. Postexposure prophylaxis is discussed in greater detail separately. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Post-exposure prophylaxis for selected individuals'.)
SPECIAL POPULATIONS
Children with special health care needs — The American Academy of Pediatrics provides information about caring for children and youth with special health care needs during the COVID-19 pandemic [204].
Closure of school may be particularly challenging for children and youth with special health care needs, who were receiving services at school (eg, speech therapy, behavior, mental health services) and/or have barriers to remote learning (eg, lack of access to a laptop/tablet or the internet, language barrier) [205]. In the United States, pediatric health care providers can review the child's Individualized Education Program to help the caregiver determine what services the child should be receiving (including compensatory services). A fact sheet from the Department of Education provides additional information. (See "Definitions of specific learning disability and laws pertaining to learning disabilities in the United States", section on 'Individuals with Disabilities Education Act'.)
Children with attention deficit hyperactivity disorder — The European attention deficit hyperactivity disorder (ADHD) guidelines group provides guidance for management of ADHD during the COVID-19 pandemic and guidance for starting stimulants or atomoxetine in children who did not have an in-person cardiovascular assessment before the pandemic [206,207].
The AAP provides suggestions to support students with ADHD and their families during the COVID-19 pandemic [208].
Children with rheumatic disease — The American College of Rheumatology has issued guidance regarding ongoing management of rheumatic disease in children during the COVID-19 pandemic according to their clinical status (eg, without exposure or infection, with close/household exposure, with asymptomatic infection, with symptomatic infection) [209].
Children involved with the child welfare system — The AAP provides guidance for children and families involved with the child welfare system during the COVID-19 pandemic [210].
ADDRESSING OR MITIGATING INDIRECT EFFECTS OF THE PANDEMIC
Disruption of immunization — Although the United States Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) consider routine vaccination an essential preventive care service that should not be delayed because of the COVID-19 pandemic, routine immunization of children and adolescents has decreased [211-217]. Disruption of immunization services increases the risk of outbreaks of vaccine-preventable illnesses [218-220]. (See 'Should routine health supervision appointments be rescheduled?' above.)
Adherence to recommendations for infants born to women who are hepatitis B surface antigen (HBsAg) positive or whose HBsAg status is unknown is particularly important for prevention of mother-to-child transmission of hepatitis B virus, especially if the delivery occurs at an unplanned facility or is attended by staff who are not knowledgeable about managing infants born to mothers who are HBsAg positive [221]. (See "Standard immunizations for children and adolescents: Overview", section on 'Benefits of vaccines' and "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Routine infant immunization'.)
Resources and guidance related to continuation of immunization during the pandemic are available from multiple professional groups, including the American Academy of Pediatrics (AAP), the Immunization Action Coalition, and the CDC.
Prolonged social isolation — Although prolonged social isolation and home confinement may provide an opportunity to enhance caregiver-child relationships, it may adversely affect children's physical and mental health [222-239]. They may be less physically active, spend more time with electronic devices, eat a poorer quality diet, be at increased risk to witness or experience family violence, and be at increased risk for injury at home, including firearm injury and intentional or unintentional ingestion [240-249]. Mental health stressors include fear of infection, boredom, and social isolation. In observational studies of school-age children and adolescents, COVID-19-related school closure/remote learning was associated with increased symptoms of depression, nonsuicidal self-injury, suicidality, anxiety, disordered eating, and/or insomnia [250-254]. In a meta-analysis of 29 studies including >80,000 children ≤18 years of age, 25 percent had clinically elevated depression symptoms and 20 percent had clinically elevated anxiety symptoms, approximately twice prepandemic estimates [253]. During the pandemic, the rates of emergency department visits for suicidality and positive primary care screening tests for symptoms of depression and suicide risk increased among adolescents and young adults [252,255]. School closures related to health emergencies also have been associated with increased risk of violence and vulnerability and decreased referrals to child protective services [225,256-258]. Vulnerable children and adolescents (eg, those who are homeless or in foster care; have a history of maltreatment; are lesbian, gay, bisexual, gender diverse, queer, questioning) are at particular risk for violence and adverse mental health effects [230].
Adverse mental and physical health effects can be mitigated and caregiver-child relations enhanced through caregiver role-modeling of healthy behaviors, involving children in family activities, promotion of self-discipline and self-sufficiency skills, and having direct, developmentally appropriate conversations with children about the pandemic [222,227,259-261].
Clinicians should consider the potential for violence and look for signs of caregiver stress, irritability, depression, and/or harsh responses to child behaviors during each clinical encounter [256]. They should ask about caregiver stress levels, methods to manage stress, social supports, and substance use. Clinicians can offer coping strategies (eg, deep breathing, calling a friend or family member), resources, and/or referrals to mental health providers to families who may benefit from these interventions.
●Resources related to child care, emotional and behavioral health needs, and prevention of violence
•American Academy of Pediatrics guidance on supporting the emotional and behavioral health needs during the COVID-19 pandemic [163]
•Global Partnership to End Violence Against Children
•The National Child Traumatic Stress Network
●Resources related to physical activity and nutrition
•American Academy of Pediatrics guidance on return to sports and physical activity
•American Academy of Pediatrics guidance on obesity management and treatment during COVID-19
●Resources for talking with children about COVID-19
•The American Academy of Child and Adolescent Psychiatry
•The AAP: Talking to children about COVID-19
•Coronavirus: A book for children (written by Elizabeth Jenner, Kate Wilson, and Nia Roberts; illustrated by Axel Scheffler)
•COVIBOOK for children younger than seven years
•The CDC
•The National Association of School Psychologists
•The United Nations Office for the Coordination of Humanitarian Affairs Inter-Agency Standing Committee (My Hero is You, Storybook for Children on COVID-19, for children approximately 6 to 11 years of age)
●Resources for home schooling children and keeping them occupied during the pandemic [177,225]
•AAP: Working and learning from home during the COVID-19 outbreak
•AAP: Getting children outside while social distancing for COVID-19
•AAP: Teens and COVID-19: Challenges and opportunities during the outbreak
•Common Sense: Wide Open School
•National Association for the Education of Young Children
•Opening Doors/Abriendo Puertas
•United Nations Children's Fund (UNICEF)
•The WHO
Loss of a parent or caregiver — Between March 2020 and October 2021, an estimated ≥5.2 million children around the world experienced the death of a parent/caregiver, custodial grandparent, coresident grandparent, or other coresident relative, including ≥187,000 children in the United States [262]. In the United States, loss of a parent or caregiver has disproportionately affected Hispanic, Black, and Native American, including Alaska Native, children [263].
Loss of a caregiver is an adverse childhood experience and may affect long-term health and well-being [264]. Adverse effects may be mitigated through programs that promote safe, stable, nurturing relationships [265].
Resources for grieving children are available from [266]:
●The American Academy of Pediatrics and the Children's Hospital of Philadelphia
●The National Child Traumatic Stress Network
Strategies for mitigating long-term effects of adverse childhood experiences are discussed in:
●The AAP clinical report on trauma-informed care
Preparing children and adolescents for the loss of a loved one is discussed separately. (See "Preparing children and adolescents for the loss of a loved one".)
IN-PERSON SCHOOL AND CHILD CARE — The emergence and predominance of the highly transmissible variants (eg, Delta [B.1.617.2], Omicron [B.1.1.529]) may result in increased school-related transmission, particularly among unvaccinated students and staff members, without strict adherence to multiple mitigation measures, including mask wearing [267-270]. Additional measures may be necessary to prevent transmission between teachers/staff and from teachers/staff to household contacts [271-274]. Observational studies before the emergence of variants of concern (table 2) suggested that in-person learning could occur without substantial effects on community transmission, particularly if eligible individuals were vaccinated and multilayer mitigation measures were implemented [275-293].
A number of professional organizations provide guidance regarding in-person school and child care attendance, including the:
●ABC Science Collaborative, developed by the Duke School of Medicine and the Duke Clinical Research Institute
●American Academy of Pediatrics (AAP) [294], which provides specific guidance on:
•Safe transportation in motor vehicles [295]
•Child care [296]
●The Centers for Disease Control and Prevention (CDC) guidance for COVID-19 prevention in kindergarten (K)-12 schools [281]
●CDC COVID-19 guidance for operating early care and education/child care programs [297]
●CDC toolkit for responding to COVID-19 cases in schools (kindergarten through 12th grade) [298]
●The eSchool+ Initiative, a cross-disciplinary collaboration from Johns Hopkins University
●National Academies of Sciences, Engineering, and Medicine [299]
●Washington University Pediatric and Adolescent Ambulatory Research Consortium [300]
●World Health Organization (WHO) [301]
•Considerations for school-related public health measures in context of COVID-19
Key recommendations include [281,283,294,299,301-303]:
●Promotion of vaccination for eligible staff and students [289]
●Inclusion of multiple perspectives (eg, public health and infectious disease experts, educators, parents/caregivers, teachers, community leaders) and permits regional variation.
●Having training and safeguards in place (eg, protocols and necessary supplies and personnel for hand hygiene, mask or cloth face coverings, physical distancing, cleaning, disinfection, ventilation, symptom screening and/or testing). Multilayered mitigation strategies are particularly important with widespread circulation of highly transmissible variants (eg, Delta [B.1.617.2], Omicron [B.1.1.529]) [304].
Observational studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission rates in schools are low with physical distancing of approximately ≥3 feet (0.9 meters) [275-277,282,305-312], provided that other mitigation measures are in place. Although retrospective case rates among students and staff were similar whether eligible school districts in Massachusetts planned to implement a minimum physical distance of ≥3 feet or ≥6 feet [313], this finding must be interpreted with caution [314-316]. Other factors (eg, transmission in the community, mask-wearing, ventilation, ability to cohort students, exposure time) may play a larger role in transmission than physical distance [290,317]. In addition, the study preceded the emergence of variants of concern, such as Beta (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529) (table 2), which have been associated with school-related transmission [304,318].
Physical distance recommendations from professional groups differ: The WHO recommends ≥3.3 feet (1 meter) [319]; the CDC and AAP recommend ≥3 or 6 feet (0.9 or 1.8 meters) depending on circumstances (eg, 6 feet between adults, between adults and students, and for middle and high school students in areas with high community transmission if cohorting is not possible) [281,294].
In the school or child care setting, the CDC recommends that masks be worn indoors by all individuals ≥2 years of age, including those who are up to date with their COVID-19 vaccinations, in areas where the COVID-19 community level is high [170].
●Establishing a protocol for monitoring and responding to changes in transmission in the school or community as well as children with COVID-19 symptoms or exposure [283,300]. The CDC provides recommendations for screening unvaccinated/incompletely vaccinated students related to the rate of transmission in the community and for screening unvaccinated/incompletely vaccinated teachers and staff independent of the rate of transmission in the community [281,283]. Students, teachers, and staff should be screened with tests for SARS-CoV-2 rather than by asking about symptoms.
●Providing realistic and practical mitigation strategies with flexibility to accommodate different types of students (eg, young children, those with developmental disabilities), classroom/school environments (eg, size, ventilation), and other factors.
●Consideration of the benefits and risks for all concerned parties (students, staff, parents/caregivers, community); the magnitude of benefits and risks may differ for students and teachers/staff. In addition to education, schools provide services to children with special health care needs, meals, opportunities to develop social/emotional skills, and physical activity. In a 2018 national survey, approximately 50 percent of adult teachers and adults living with school-aged children had conditions that are considered definite or possible risk factors for severe COVID-19 [320].
●Special considerations for vulnerable populations (eg, those with developmental challenges, those who are medically fragile or live in poverty) [321].
The eSchool+ Initiative provides a tracker that categorizes school reopening plans according to consideration of 12 categories (eg, core academics, SARS-CoV-2 protection, food and nutrition, caregiver choice, teacher and staff choice, children of poverty and disadvantage).
SPORTS AND EXTRACURRICULAR ACTIVITIES — Centers for Disease Control and Prevention (CDC) guidance recommends that individuals who live in areas with high COVID-19 community levels wear a mask indoors in public [168-170]. In areas with moderate or low COVID-19 community levels, children and adolescents should follow local regulations.
Decisions about participation in sports and extracurricular activities for children and adolescents who are not up to date with their COVID-19 vaccinations should be made on a case-by-case basis [283,322]. Factors to consider include the ability to maintain mitigation measures (eg, physical distance, mask wearing, ventilation) and whether the activities increase the risk of transmission among students or staff (eg, by resulting in or requiring deep breathing [eg, intense exercise, shouting, singing]). Observational studies suggest that the risk of transmission is lower with outdoor than indoor sports activity [323]. Although indoor sports (eg, wrestling, gymnastics, ice hockey), close contact team sports, and intense exercise have been associated with increased transmission [200,273,324-327], there are reports of successful implementation of stringent mitigation protocols [328]. Social gatherings associated with team sports also may increase the risk of transmission [322].
Return to play or strenuous activity following infection is discussed separately. (See "COVID-19: Return to play or strenuous activity following infection".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: COVID-19 – Index of guideline topics".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)
●Basics topics (see "Patient education: COVID-19 and children (The Basics)" and "Patient education: COVID-19 overview (The Basics)" and "Patient education: COVID-19 vaccines (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Children with COVID-19 and severe or critical lower respiratory tract disease generally require hospital admission. Severe disease is defined by a new requirement for supplemental oxygen or increased requirement from baseline without new or increased need for ventilatory support (noninvasive or invasive). Critical disease is defined by new or increased need for noninvasive or invasive mechanical ventilation, sepsis, multiorgan failure, or rapidly worsening clinical trajectory. (See 'Assessment of severity' above.)
●Supportive care (eg, respiratory support, fluid and electrolyte support, monitoring for cytokine release syndrome) is the mainstay of therapy for children with severe or critical COVID-19. (See 'Supportive care for all patients' above.)
●We agree with recommendations from the multicenter interim guidance on the use of antiviral agents for children with COVID-19 and other experts that antiviral therapy should be considered on a case-by-case basis and preferably occur in the context of a clinical trial, if a clinical trial is available. (See 'SARS-CoV-2 antiviral therapy for select patients' above.)
•Decisions regarding antiviral therapy should be individualized according to disease severity, clinical trajectory, and underlying conditions that may increase the risk for progression.
•When a decision is made to use antiviral therapy in a hospitalized child who cannot be enrolled in a clinical trial, we suggest remdesivir rather than other antiviral agents (Grade 2C). Randomized trials in adults suggest a potential benefit.
•We recommend not using hydroxychloroquine or chloroquine (Grade 1B). Their emergency use authorization has been revoked, their clinical benefit is unproven, and they have potential toxicity.
●For hospitalized children who cannot be enrolled in a clinical trial, we make decisions about the use of adjunctive therapies for immune-mediated complications (eg, glucocorticoids, interleukin-6 inhibitors) of COVID-19 on a case-by-case basis. (See 'Individualized adjunctive therapy' above.)
●Children with documented or suspected COVID-19 and mild symptoms (eg, fever, cough, pharyngitis, other respiratory symptoms) generally should be managed at home unless they have a chronic condition that increases their risk of severe disease. Decisions regarding outpatient antiviral or monoclonal therapy are made on a case-by-case basis. Additional management is focused on prevention of transmission to others (ie, isolation), monitoring for clinical deterioration (eg, difficulty breathing, cyanosis, symptoms of shock), and supportive care. (See 'Outpatient therapy for select children' above and 'How should children be managed at home?' above.)
●Symptomatic care for COVID-19 in the outpatient setting is similar to that for other upper respiratory or gastrointestinal clinical syndromes. It is discussed separately. (See "The common cold in children: Management and prevention", section on 'Symptomatic therapy' and "Acute pharyngitis in children and adolescents: Symptomatic treatment", section on 'Symptomatic treatment' and "Fever in infants and children: Pathophysiology and management", section on 'Management of fever' and "Acute viral gastroenteritis in children in resource-rich countries: Management and prevention", section on 'Management'.)
●Prevention of transmission focuses on hygiene and social distancing. The Centers for Disease Control and Prevention and World Health Organization provide guidance about preventing transmission of COVID-19 in the home and outpatient setting. (See 'Prevention of transmission' above.)
●Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization is the optimal method of pre-exposure prophylaxis for eligible individuals. Pre-exposure prophylaxis with copackaged tixagevimab-cilgavimab may be warranted on a case-by-case basis. (See 'Pre-exposure prophylaxis' above.)
●Management of COVID-19 in children also encompasses management of indirect effects, particularly adverse physical and mental health effects of prolonged home confinement (eg, decreased physical activity, poorer quality diet, social isolation, increased risk of violence). (See 'Addressing or mitigating indirect effects of the pandemic' above.)
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9 : Multicenter Interim Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.
10 : Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists.
11 : Ibuprofen use and clinical outcomes in COVID-19 patients.
12 : Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study.
13 : Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts.
14 : Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19.
15 : Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study.
16 : Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study.
17 : Risk of SARS-CoV-2 Infection and COVID-19 Severity Associated With Exposure to Nonsteroidal Anti-Inflammatory Drugs: Systematic Review and Meta-Analysis.
18 : ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic: The Pediatric Perspective.
19 : ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic: The Pediatric Perspective.
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23 : ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic: The Pediatric Perspective.
24 : ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic: The Pediatric Perspective.
25 : The severity of COVID-19 in children on immunosuppressive medication.
26 : COVID-19 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto group of ESPGHAN.
27 : Infection in solid-organ transplant recipients.
28 : Infection in Organ Transplantation.
29 : Infection in Organ Transplantation.
30 : Clinical Outcomes of Coronavirus Disease 2019 With Evidence-based Supportive Care.
31 : Mild or Moderate Covid-19.
32 : Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing.
33 : Empiric Antibacterial Therapy and Community-onset Bacterial Coinfection in Patients Hospitalized With Coronavirus Disease 2019 (COVID-19): A Multi-hospital Cohort Study.
34 : An observational cohort study of bacterial co-infection and implications for empirical antibiotic therapy in patients presenting with COVID-19 to hospitals in North West London.
35 : Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study.
36 : Consensus-based clinical recommendations and research priorities for anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illness.
37 : Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C.
38 : Prevalence of thrombotic complications in children with SARS-CoV-2.
39 : Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review.
40 : A Call for Pediatric COVID-19 Clinical Trials.
41 : Compassionate Use of Remdesivir for Patients with Severe Covid-19.
42 : A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.
43 : Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.
44 : Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro.
45 : Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses.
46 : Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection.
47 : Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection.
48 : A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics.
49 : A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics.
50 : Remdesivir for the Treatment of Covid-19 - Final Report.
51 : Comparison of Time to Clinical Improvement With vs Without Remdesivir Treatment in Hospitalized Patients With COVID-19.
52 : 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.
53 : Update Alert: Should Remdesivir Be Used for the Treatment of Patients With COVID-19? Rapid, Living Practice Points From the American College of Physicians (Version 2).
54 : Remdesivir treatment in hospitalized patients with COVID-19: a comparative analysis of in-hospital all-cause mortality in a large multi-center observational cohort.
55 : Update Alert 2: Remdesivir for Adults With COVID-19.
56 : Update Alert 2: Remdesivir for Adults With COVID-19.
57 : A living WHO guideline on drugs for covid-19.
58 : Update to living WHO guideline on drugs for covid-19.
59 : Update to living WHO guideline on drugs for covid-19.
60 : Update to living WHO guideline on drugs for covid-19.
61 : Update to living WHO guideline on drugs for covid-19.
62 : Remdesivir for the treatment of COVID-19.
63 : Remdesivir for the treatment of COVID-19.
64 : Remdesivir for the treatment of COVID-19.
65 : Remdesivir for the treatment of COVID-19.
66 : Remdesivir for 5 or 10 Days in Patients with Severe Covid-19.
67 : Compassionate Use of Remdesivir in Children With Severe COVID-19.
68 : Sinus Bradycardia in a Pediatric Patient Treated With Remdesivir for Acute Coronavirus Disease 2019: A Case Report and a Review of the Literature.
69 : Severe sinus bradycardia associated with Remdesivir in a child with severe SARS-CoV-2 infection.
70 : Sinus Bradycardia in Children Treated With Remdesivir for COVID-19.
71 : Remdesivir, Sinus Bradycardia and Therapeutic Drug Monitoring in Children With Severe COVID-19.
72 : Remdesivir, Sinus Bradycardia and Therapeutic Drug Monitoring in Children With Severe COVID-19.
73 : Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.
74 : Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial.
75 : Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial.
76 : Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial.
77 : Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial.
78 : Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19.
79 : Update Alert 3: Hydroxychloroquine or Chloroquine for the Treatment or Prophylaxis of COVID-19.
80 : Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.
81 : Reported Adverse Drug Reactions Associated With the Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic.
82 : Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis.
83 : Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review.
84 : Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review.
85 : Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.
86 : Multidisciplinary Guidance Regarding the Use of Immunomodulatory Therapies for Acute Coronavirus Disease 2019 in Pediatric Patients.
87 : Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis.
88 : Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis.
89 : Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis.
90 : Dexamethasone in Hospitalized Patients with Covid-19.
91 : Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial.
92 : Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial.
93 : Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.
94 : Systemic corticosteroids for the treatment of COVID-19.
95 : Systemic corticosteroids for the treatment of COVID-19.
96 : 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host.
97 : Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.
98 : Immune Immunomodulation in Coronavirus Disease 2019 (COVID-19): Strategic Considerations for Personalized Therapeutic Intervention.
99 : Treatment of patients with nonsevere and severe coronavirus disease 2019: an evidence-based guideline.
100 : The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis.
101 : Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review.
102 : Drug treatments for covid-19: living systematic review and network meta-analysis.
103 : Update to living systematic review on drug treatments for covid-19.
104 : Update to living systematic review on drug treatments for covid-19.
105 : Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis.
106 : Safety and Antibody Kinetics of COVID-19 Convalescent Plasma for the Treatment of Moderate to Severe Cases of SARS-CoV-2 Infection in Pediatric Patients.
107 : Efficacy of High-Dose Polyclonal Intravenous Immunoglobulin in COVID-19: A Systematic Review.
108 : A randomized, controlled trial of vitamin A in children with severe measles.
109 : A randomized, controlled trial of vitamin A in children with severe measles.
110 : A randomized, controlled trial of vitamin A in children with severe measles.
111 : Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents.
112 : Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents.
113 : Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents.
114 : Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.
115 : Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.
116 : Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.
117 : Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.
118 : Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.
119 : SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19.
120 : Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19.
121 : REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19.
122 : Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab.
123 : Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial.
124 : The impact of neutralizing monoclonal antibodies on the outcomes of COVID-19 outpatients: A systematic review and meta-analysis of randomized controlled trials.
125 : Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of Coronavirus Disease 2019 in Children and Adolescents.
126 : SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
127 : SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
128 : SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
129 : SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
130 : SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
131 : SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
132 : Sequelae of COVID-19 in Hospitalized Children: A 4-Months Follow-Up.
133 : SARS-CoV-2-Associated Deaths Among Persons Aged<21 Years - United States, February 12-July 31, 2020.
134 : Covid-19: a remote assessment in primary care.
135 : Covid-19: a remote assessment in primary care.
136 : Characteristics of Viral Shedding Time in SARS-CoV-2 Infections: A Systematic Review and Meta-Analysis.
137 : Symptomatic Infection is Associated with Prolonged Duration of Viral Shedding in Mild Coronavirus Disease 2019: A Retrospective Study of 110 Children in Wuhan.
138 : Symptomatic Infection is Associated with Prolonged Duration of Viral Shedding in Mild Coronavirus Disease 2019: A Retrospective Study of 110 Children in Wuhan.
139 : Symptomatic Infection is Associated with Prolonged Duration of Viral Shedding in Mild Coronavirus Disease 2019: A Retrospective Study of 110 Children in Wuhan.
140 : Commentary: Myths and facts on vitamin D amidst the COVID-19 pandemic.
141 : Commentary: Myths and facts on vitamin D amidst the COVID-19 pandemic.
142 : Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results.
143 : Sorting Out Whether Vitamin D Deficiency Raises COVID-19 Risk.
144 : Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.
145 : Is vitamin D deficiency a risk factor for COVID-19 in children?
146 : Assessment of the Association of Vitamin D Level With SARS-CoV-2 Seropositivity Among Working-Age Adults.
147 : Effect of Oral Azithromycin vs Placebo on COVID-19 Symptoms in Outpatients With SARS-CoV-2 Infection: A Randomized Clinical Trial.
148 : Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial.
149 : Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis.
150 : Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis.
151 : Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis.
152 : Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis.
153 : Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis.
154 : Risk for Newly Diagnosed Diabetes>30 Days After SARS-CoV-2 Infection Among Persons Aged<18 Years - United States, March 1, 2020-June 28, 2021.
155 : New-onset type 1 diabetes in Finnish children during the COVID-19 pandemic.
156 : Prevalence of Select New Symptoms and Conditions Among Persons Aged Younger Than 20 Years and 20 Years or Older at 31 to 150 Days After Testing Positive or Negative for SARS-CoV-2.
157 : Prevalence of Select New Symptoms and Conditions Among Persons Aged Younger Than 20 Years and 20 Years or Older at 31 to 150 Days After Testing Positive or Negative for SARS-CoV-2.
158 : Long COVID and kids: scientists race to find answers.
159 : How Common is Long COVID in Children and Adolescents?
160 : Long COVID symptoms in SARS-CoV-2-positive adolescents and matched controls (LongCOVIDKidsDK): a national, cross-sectional study.
161 : Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study.
162 : Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study.
163 : Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study.
164 : Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study.
165 : Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study.
166 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
167 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
168 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
169 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
170 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
171 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
172 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
173 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
174 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
175 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
176 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
177 : Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.
178 : Covid-19: Don't forget the impact on US family physicians.
179 : Covid-19: Don't forget the impact on US family physicians.
180 : Covid-19: Don't forget the impact on US family physicians.
181 : Covid-19: Don't forget the impact on US family physicians.
182 : Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.
183 : Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.
184 : Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.
185 : Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.
186 : Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.
187 : Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.
188 : Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.
189 : Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.
190 : Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.
191 : Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.
192 : Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020.
193 : Serious Adverse Health Events, Including Death, Associated with Ingesting Alcohol-Based Hand Sanitizers Containing Methanol - Arizona and New Mexico, May-June 2020.
194 : Serious Adverse Health Events, Including Death, Associated with Ingesting Alcohol-Based Hand Sanitizers Containing Methanol - Arizona and New Mexico, May-June 2020.
195 : Pediatric Eye Injuries by Hydroalcoholic Gel in the Context of the Coronavirus Disease 2019 Pandemic.
196 : Hand Sanitizer-Induced Ocular Injury: A COVID-19 Hazard in Children.
197 : Hand sanitizer associated ocular chemical injury: A mini-review on its rise under COVID-19.
198 : Hand sanitizer associated ocular chemical injury: A mini-review on its rise under COVID-19.
199 : Tixagevimab and Cilgavimab (Evusheld) for Pre-Exposure Prophylaxis of COVID-19.
200 : SARS-CoV-2 B.1.617.2 (Delta) Variant COVID-19 Outbreak Associated with a Gymnastics Facility - Oklahoma, April-May 2021.
201 : A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19.
202 : Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial.
203 : A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19.
204 : A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19.
205 : A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19.
206 : ADHD management during the COVID-19 pandemic: guidance from the European ADHD Guidelines Group.
207 : Starting ADHD medications during the COVID-19 pandemic: recommendations from the European ADHD Guidelines Group.
208 : Starting ADHD medications during the COVID-19 pandemic: recommendations from the European ADHD Guidelines Group.
209 : American College of Rheumatology Guidance for the Management of Pediatric Rheumatic Disease During the COVID-19 Pandemic: Version 2.
210 : American College of Rheumatology Guidance for the Management of Pediatric Rheumatic Disease During the COVID-19 Pandemic: Version 2.
211 : Effects of the COVID-19 Pandemic on Routine Pediatric Vaccine Ordering and Administration - United States, 2020.
212 : Decline in Child Vaccination Coverage During the COVID-19 Pandemic - Michigan Care Improvement Registry, May 2016-May 2020.
213 : Number of Childhood and Adolescent Vaccinations Administered Before and After the COVID-19 Outbreak in Colorado.
214 : Pediatric Vaccination During the COVID-19 Pandemic.
215 : Impact of the COVID-19 Pandemic on Administration of Selected Routine Childhood and Adolescent Vaccinations - 10 U.S. Jurisdictions, March-September 2020.
216 : Association of the COVID-19 Pandemic With Routine Childhood Vaccination Rates and Proportion Up to Date With Vaccinations Across 8 US Health Systems in the Vaccine Safety Datalink.
217 : Routine Vaccination Coverage - Worldwide, 2020.
218 : Routine Vaccination Coverage - Worldwide, 2020.
219 : Routine Vaccination Coverage - Worldwide, 2020.
220 : Routine Vaccination Coverage - Worldwide, 2020.
221 : Routine Vaccination Coverage - Worldwide, 2020.
222 : Mitigate the effects of home confinement on children during the COVID-19 outbreak.
223 : Understanding differences between summer vs. school obesogenic behaviors of children: the structured days hypothesis.
224 : The psychological impact of quarantine and how to reduce it: rapid review of the evidence.
225 : Parenting in a time of COVID-19.
226 : Mitigating the Impacts of the COVID-19 Pandemic Response on At-Risk Children.
227 : Mitigating the Impacts of the COVID-19 Pandemic Response on At-Risk Children.
228 : Pandemic school closures: risks and opportunities.
229 : Mental Health Status Among Children in Home Confinement During the Coronavirus Disease 2019 Outbreak in Hubei Province, China.
230 : Vulnerable Youth and the COVID-19 Pandemic.
231 : Risks to children and young people during covid-19 pandemic.
232 : Behavioral and Emotional Disorders in Children during the COVID-19 Epidemic.
233 : Mental health effects of school closures during COVID-19.
234 : Association of Children's Mode of School Instruction with Child and Parent Experiences and Well-Being During the COVID-19 Pandemic - COVID Experiences Survey, United States, October 8-November 13, 2020.
235 : Medical Admissions Among Adolescents With Eating Disorders During the COVID-19 Pandemic.
236 : Longitudinal Trends in Body Mass Index Before and During the COVID-19 Pandemic Among Persons Aged 2-19 Years - United States, 2018-2020.
237 : The Association Between School Closures and Child Mental Health During COVID-19.
238 : Covid-19: Pandemic has disproportionately harmed children's mental health, report finds.
239 : Pediatric Emergency Department Visits Associated with Mental Health Conditions Before and During the COVID-19 Pandemic - United States, January 2019-January 2022.
240 : Firearms Injuries Involving Young Children in the United States During the COVID-19 Pandemic.
241 : Pediatric Firearm-Related Hospital Encounters During the SARS-CoV-2 Pandemic.
242 : Lockdown: more domestic accidents than COVID-19 in children.
243 : Adolescents' Substance Use and Physical Activity Before and During the COVID-19 Pandemic.
244 : COVID-19 and Pediatric Ingestions.
245 : Children Witnessing Domestic and Family Violence: A Widespread Occurrence during the Coronavirus Disease 2019 (COVID-19) Pandemic.
246 : Association of COVID-19 Mitigation Measures With Changes in Cardiorespiratory Fitness and Body Mass Index Among Children Aged 7 to 10 Years in Austria.
247 : Changes in Body Mass Index Among Children and Adolescents During the COVID-19 Pandemic.
248 : Screen Time Use Among US Adolescents During the COVID-19 Pandemic: Findings From the Adolescent Brain Cognitive Development (ABCD) Study.
249 : Association of Changes in Obesity Prevalence With the COVID-19 Pandemic in Youth in Massachusetts.
250 : Assessment of Mental Health of High School Students During Social Distancing and Remote Schooling During the COVID-19 Pandemic in Austria.
251 : Young people's mental health during the COVID-19 pandemic.
252 : COVID-19 and Adolescent Depression and Suicide Risk Screening Outcomes.
253 : Global Prevalence of Depressive and Anxiety Symptoms in Children and Adolescents During COVID-19: A Meta-analysis.
254 : Suicide Risk in Adolescents During the COVID-19 Pandemic.
255 : Emergency Department Visits for Suspected Suicide Attempts Among Persons Aged 12-25 Years Before and During the COVID-19 Pandemic - United States, January 2019-May 2021.
256 : Increased Risk for Family Violence During the COVID-19 Pandemic.
257 : Rise in the incidence of abusive head trauma during the COVID-19 pandemic.
258 : Who has been missed? Dramatic decrease in numbers of children seen for child protection assessments during the pandemic.
259 : Parenting as Primary Prevention.
260 : Parenting as Primary Prevention.
261 : Protecting the psychological health of children through effective communication about COVID-19.
262 : Global, regional, and national minimum estimates of children affected by COVID-19-associated orphanhood and caregiver death, by age and family circumstance up to Oct 31, 2021: an updated modelling study.
263 : COVID-19-Associated Orphanhood and Caregiver Death in the United States.
264 : COVID-19-Associated Orphanhood and Caregiver Death in the United States.
265 : Trauma-Informed Care.
266 : Thousands of US Youths Cope With the Trauma of Losing Parents to COVID-19.
267 : Outbreak Associated with SARS-CoV-2 B.1.617.2 (Delta) Variant in an Elementary School - Marin County, California, May-June 2021.
268 : Association Between K-12 School Mask Policies and School-Associated COVID-19 Outbreaks - Maricopa and Pima Counties, Arizona, July-August 2021.
269 : Pediatric COVID-19 Cases in Counties With and Without School Mask Requirements - United States, July 1-September 4, 2021.
270 : COVID-19 Incidence Among 6th-12th Grade Students by Vaccination Status.
271 : Clusters of SARS-CoV-2 Infection Among Elementary School Educators and Students in One School District - Georgia, December 2020-January 2021.
272 : The effects of school closures on SARS-CoV-2 among parents and teachers.
273 : Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in a Georgia School District-United States, December 2020-January 2021.
274 : Coronavirus Disease 2019 Cluster Originating in a Primary School Teachers' Room in Japan.
275 : Minimal transmission of SARS-CoV-2 from paediatric COVID-19 cases in primary schools, Norway, August to November 2020.
276 : Incidence and Secondary Transmission of SARS-CoV-2 Infections in Schools.
277 : COVID-19 Cases and Transmission in 17 K-12 Schools - Wood County, Wisconsin, August 31-November 29, 2020.
278 : The role of children in the transmission of SARS-CoV2: updated rapid review.
279 : Transmission of SARS-CoV-2 in children aged 0 to 19 years in childcare facilities and schools after their reopening in May 2020, Baden-Württemberg, Germany.
280 : Novel Coronavirus 2019 Transmission Risk in Educational Settings.
281 : Novel Coronavirus 2019 Transmission Risk in Educational Settings.
282 : SARS-CoV-2 infection and transmission in educational settings: a prospective, cross-sectional analysis of infection clusters and outbreaks in England.
283 : SARS-CoV-2 infection and transmission in educational settings: a prospective, cross-sectional analysis of infection clusters and outbreaks in England.
284 : School reopening without robust COVID-19 mitigation risks accelerating the pandemic.
285 : Severe Acute Respiratory Syndrome Coronavirus 2 Infections in Primary School Age Children After Partial Reopening of Schools in England.
286 : Minimal SARS-CoV-2 Transmission After Implementation of a Comprehensive Mitigation Strategy at a School - New Jersey, August 20-November 27, 2020.
287 : Preventing COVID-19 Transmission in Education Settings.
288 : COVID-19 Transmission during Transportation of 1st to 12th Grade Students: Experience of an Independent School in Virginia.
289 : SARS-CoV-2 Infection in Public School District Employees Following a District-Wide Vaccination Program - Philadelphia County, Pennsylvania, March 21-April 23, 2021.
290 : Community SARS-CoV-2 Surge and Within-School Transmission.
291 : Reopening Schools and the Dynamics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infections in Israel: A Nationwide Study.
292 : The impact of school opening model on SARS-CoV-2 community incidence and mortality.
293 : Measures implemented in the school setting to contain the COVID-19 pandemic
294 : Measures implemented in the school setting to contain the COVID-19 pandemic
295 : Measures implemented in the school setting to contain the COVID-19 pandemic
296 : Measures implemented in the school setting to contain the COVID-19 pandemic
297 : Measures implemented in the school setting to contain the COVID-19 pandemic
298 : Measures implemented in the school setting to contain the COVID-19 pandemic
299 : Measures implemented in the school setting to contain the COVID-19 pandemic
300 : Practical School Algorithms for Symptomatic or SARS-CoV-2-Exposed Students Are Essential for Returning Children to In-Person Learning.
301 : Practical School Algorithms for Symptomatic or SARS-CoV-2-Exposed Students Are Essential for Returning Children to In-Person Learning.
302 : The Urgency and Challenge of Opening K-12 Schools in the Fall of 2020.
303 : Household COVID-19 risk and in-person schooling.
304 : Delineation of the intimate details of the backbone conformation of pyridine nucleotide coenzymes in aqueous solution.
305 : Transmission of SARS-CoV-2 in Australian educational settings: a prospective cohort study.
306 : Surveillance of COVID-19 school outbreaks, Germany, March to August 2020.
307 : Data-Driven Reopening of Urban Public Education Through Chicago's Tracking of COVID-19 School Transmission.
308 : Low SARS-CoV-2 Transmission in Elementary Schools - Salt Lake County, Utah, December 3, 2020-January 31, 2021.
309 : Pilot Investigation of SARS-CoV-2 Secondary Transmission in Kindergarten Through Grade 12 Schools Implementing Mitigation Strategies - St. Louis County and City of Springfield, Missouri, December 2020.
310 : COVID-19 in Primary and Secondary School Settings During the First Semester of School Reopening - Florida, August-December 2020.
311 : Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis.
312 : COVID-19 Case Rates in Transitional Kindergarten Through Grade 12 Schools and in the Community - Los Angeles County, California, September 2020-March 2021.
313 : Effectiveness of 3 Versus 6 ft of Physical Distancing for Controlling Spread of Coronavirus Disease 2019 Among Primary and Secondary Students and Staff: A Retrospective, Statewide Cohort Study.
314 : Schools and Coronavirus Disease 2019 Prevention.
315 : Six Feet and the Classroom.
316 : Assess Ventilation When Determining Safe Distancing in Schools to Control Coronavirus Disease 2019 (COVID-19) Transmission.
317 : Mask Use and Ventilation Improvements to Reduce COVID-19 Incidence in Elementary Schools - Georgia, November 16-December 11, 2020.
318 : Mask Use and Ventilation Improvements to Reduce COVID-19 Incidence in Elementary Schools - Georgia, November 16-December 11, 2020.
319 : Mask Use and Ventilation Improvements to Reduce COVID-19 Incidence in Elementary Schools - Georgia, November 16-December 11, 2020.
320 : Risk for Severe COVID-19 Illness Among Teachers and Adults Living With School-Aged Children.
321 : Children With Disabilities Must Be More Than an Afterthought in School Reopening.
322 : Data and Policy to Guide Opening Schools Safely to Limit the Spread of SARS-CoV-2 Infection.
323 : Risk of SARS-CoV-2 transmission from on-field player contacts in amateur, youth and professional football (soccer).
324 : COVID-19 Outbreak Among Attendees of an Exercise Facility - Chicago, Illinois, August-September 2020.
325 : Community Transmission of SARS-CoV-2 at Three Fitness Facilities - Hawaii, June-July 2020.
326 : SARS-CoV-2 Transmission Associated with High School Wrestling Tournaments - Florida, December 2020-January 2021.
327 : Notes from the Field: SARS-CoV-2 Transmission Associated with High School Football Team Members - Florida, September-October 2020.
328 : Youth ice hockey COVID-19 protocols and prevention of sport-related transmission.
