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The authors note the following key points:
- The WHO has produced a definition of long COVID (post-COVID condition) for children.
- Using this definition, we found that 1/4 of adolescents at most meet the definition of long COVID over 2 years, and 7% met the definition at each time point.
- The most common persisting problems were fatigue, headache and shortness of breath.
- Risk factors for long COVID in adolescence included female sex, learning difficulties at school and family history of ongoing COVID-19 problems.

Of 27,537 children diagnosed with acute COVID-19, 14.1% developed long COVID. During a mean post-diagnosis follow-up of 12.6 months, 93.6% of children had general practitioner consultations, 93.5% had pharmacy usage, and 61.0% had medical procedures. First-year costs were highest at €823 per patient per year; 4.3% of children required caregiver-related work absenteeism.

Compared to children who did not develop long COVID, a long COVID diagnosis was associated with an incremental cost increase of €98 per patient per year. The authors recognise that the true societal burden of long COVID in children is likely underestimated since long COVID-related indirect costs are not fully captured and access to care varies.

They conclude that children living with long COVID managed in the community pose a non-neglectable burden on French health insurance, reinforcing the importance of managing long COVID with a multidisciplinary approach and optimizing resource allocation.

The authors share the following plain language summary:

"Pediatric Long COVID (PLC) can significantly affect children’s daily lives, but its impact on well-being is not yet fully understood. This study investigated the quality of life, mental health, and social well-being of children with PLC compared to those with other chronic conditions and the general population.
Using self-report questionnaires, we found that children with PLC experience worse quality of life and are at higher risk of severe anxiety, depression, and sleep problems.
These findings highlight the need for better screening and personalized care to support children with PLC. Understanding the challenges they face can help improve medical care and ensure they receive the right support for their recovery and well-being".

The authors note that significant uncertainties persist regarding the effects on various organs and systems in children. The aim of their retrospective research study was to study the clinical and functional state of the cardiovascular system in children with a history of COVID-19.

They found a notable gender imbalance with boys predominating. The clinical course was predominantly mild-to-moderate; a severe course was documented in 6.5% of cases. According to ECG interpretation, P wave and QT interval changes were observed in the acute period of COVID-19. A prospective laboratory and instrumental examination identified increased immunoglobulin G (IgG) levels in all age groups and long-term changes in ECG. The group of school-age children with cardiac complaints suffered from insufficient BP reduction at night. They also exhibited various heart rhythm disorders (35%).

They conclude that "significant cardiac changes in adolescents post-COVID-19 indicate the risk of cardiovascular complications and the need for long-term follow-up. The findings warrant further investigation, especially with regard to cardiovascular and immune changes and their long-term consequences in children who have undergone COVID-19"

Five years into the COVID-19 pandemic, long COVID in children and adolescents has emerged as a complex, chronic condition with distinct clinical features and challenges that can affect the quality of life of children and adolescents.
Pediatric patients commonly experience fatigue, cognitive dysfunction, orthostatic intolerance, and conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and mast cell activation syndrome (MCAS), often with overlapping presentations.
Effective management for pediatric long COVID requires individualized, multidisciplinary care focused on symptom relief and functional improvement. As clinical understanding continues to evolve, there remains an urgent need for standardized diagnostic tools, consistent outcome measures, and coordinated research efforts to guide treatment and improve quality of life for affected children.

The authors state that "As we look back on the COVID-19 pandemic, PIMS-TS was a rapidly emergent, novel condition with an initial high incidence of cardiovascular compromise requiring hospitalization and often intensive care support. Inter-organizational co-operation and communication lead to rapid convergence in management of the condition, and also a rapid expansion of observational studies"
The authors conclude that "Looking at overall outcome data, this was thankfully a condition with overall very low mortality and limited long term morbidity".

Multisystem inflammatory syndrome (MIS) is a severe disease that occurs weeks to months after acute infection with SARS-CoV-2, often occurring in children (MISC). Symptoms include high fever, rash, nausea, diarrhea, and abdominal pain. Children with MISC can develop cardiovascular injury including ventricular failure, coronary artery aneurysms, or shock. Current treatment strategies primarily target the hyperinflammatory response, but not the potential role of the viral spike protein.

This randomized, double-blind, placebo-controlled clinical trial tested the zonulin antagonist larazotide in 12 children with MISC with a median age of 5.7 years. No larazotide-related adverse events were reported. The concentration of SARS-CoV-2 spike protein antigen in blood samples correlated with inflammatory markers and with gastrointestinal symptoms.

Children treated with larazotide displayed faster resolution of gastrointestinal symptoms, faster clearance of spike antigen, and a faster return to usual activities.
The authors state that their "findings suggest that larazotide treatment may be safe in children and may improve resolution of symptoms when used as an adjuvant therapy for MISC"

The aim of this study was to assess children's self or parental-rated health following Aotearoa New Zealand's (NZ) first widespread community transmission of SARS-CoV-2 in February 2022.

Greater than one-fifth of NZ children reported persisting symptoms after Covid-19 infection.
Overall, the proportion of children in the survey who reported good or very good health reduced from 82.6% before NZ's two large Omicron waves to 66.9% after these waves, with changes in health significantly more frequent in those who had a Covid-19 infection compared with those who had not.

The authors note that these findings are consistent with a very large international literature describing the longer-term impacts of Covid-19 on child health. They state that "preventing infection is key to preventing post-Covid-19 symptoms" and that "An evidence-based strategy to prevent infection should include multiple components, including good ventilation and air filtration in schools/early childhood education centres, mask use and hybrid learning during outbreak peaks and a strong emphasis on staying home when sick. There is also good evidence that vaccination is protective against Long Covid"

In this study of hospital departments, virus was effectively detected in the air of a COVID Building and viral load per sampling day reached up to 1123 viral gene copies/m3.
Moreover, it was shown that negative pressure ventilation measures with HEPA filtration at the ICU and HDU areas can prevent SARS-CoV-2 airborne transmission as the virus could not be detected.
Furthermore, it was demonstrated that air cleaners using TiO2-UV light technology can reduce up to 98,1 % of viral load in the air of a COVID patient room with confirmed positive airborne viral RNA.

In general, it was shown that in combination to behavioral compliance of strict safety health protocols, and the usage of appropriate air cleaners, airborne SARS-CoV-2 transmission can be significantly controlled, thus, reducing patient days in hospital and benefit public health care systems.

The authors conducted a metabolic profiling of 147 children’s serum samples, including acute COVID-19 patients, MIS-C patients, and healthy controls.

The results revealed distinct metabolic profiles in acute COVID-19 and MIS-C patients, with significant alterations in lipid classes. Both conditions exhibited an elevated Apo-B100/Apo-A1 ratio and increased serum inflammatory markers. MIS-C patients showed unique disruptions, including increased triglycerides and altered lipoprotein composition.

Despite milder clinical respiratory symptoms, children’s metabolic disturbances mirrored those seen in severe adult COVID-19 patients, indicating a shared inflammatory response to SARS-CoV-2. This suggests potential long-term health impacts, underscoring the need for continued research into the metabolic consequences of COVID-19 in children.

This study aimed to evaluate the impact of maternal infection on neurodevelopment and investigate whether cytokine and chemokine profiles predict delays at 24 months.

The authors state that "Prenatal SARS-COV-2 infection in pregnant women is linked to developmental delays in toddlers, with cytokine and chemokine changes associated with neurodevelopmental outcomes at 24 months

This study shows the long-term impact of maternal SARS-COV-2 infection on child development, highlighting inflammatory markers like IFN-γ, TNFα, IL-6, IL-8, IL-17, IL-1β, and CXCL10."

This group previously conducted psychological and neurologic assessments of children 6 to 12 months after hospitalization for MIS-C and found reduced executive functioning, increased behavioral symptoms, and lower quality of life compared with a sibling and community control group. They followed up again up to two years after hospital discharge.
In this longitudinal, matched cohort study of children with MIS-C and controls, children with MIS-C had more somatic symptoms than control children. Overall, however, patients with MIS-C had improved neurologic and psychological outcomes between the testing intervals, performing similarly to controls on most measures by year 2 follow-up. These findings suggest that these concerns may improve over time.

Participants in this study were Japanese children younger than 18 years hospitalized for COVID-19 between November 2021 and October 2022, along with their COVID-19 affected parents.

Of 108 children enrolled, the prevalence of long-COVID was 44.9%, 37.8%, and 22.8% at 1, 3, and 6 months, respectively, after SARS-CoV-2 infection.
The study found that there were no specific risk factors for long-COVID.
Cough, fatigue, and sleep disturbance were the most common long-COVID symptoms, with sleep disturbance associated with a change in lower QOL score from admission at all three follow-ups.
The prevalence of ME/CFS symptoms among 0–6 years was significantly lower than among 7–17 years and parents; there was no significant difference between 7 and 17 years and parents.

The authors conclude that even 6 months after SARS-CoV-2 infection, 22.8% of pediatric patients still had long-COVID symptoms. Some of these symptoms were similar to those of ME/CFS, potentially affecting children's QOL.

Recent studies have identified characteristic symptom patterns of long COVID (LC) in adults and children older than 5 years. However, the authors note that LC remains poorly characterized in early childhood. This knowledge gap limits efforts to identify, care for, and prevent LC in this vulnerable population.

In this study of 472 infants/toddlers and 539 preschool-aged children, prolonged symptoms were identified that were more common in young children with infection history than those without.

Infants/toddlers (0-2 years) with infection history were more likely to experience trouble sleeping, fussiness, poor appetite, stuffy nose, and cough, and preschool-aged children (3-5 years) were more likely to experience dry cough and daytime tiredness/sleepiness or low energy.

Results of this cohort study suggest that symptom patterns were distinguishable across infants/toddlers and preschool-aged children, and from previously studied older children and adults.

The authors of this study state that "Long COVID is common, affecting up to 10% to 20% of children with a history of COVID-19. With almost 6 million US children potentially affected, this is higher than the number of children with asthma, the most common chronic health problem in children".

The RECOVER study found that signs and symptoms of Long Covid are variable in children of different ages.
Infants, toddlers, and preschool-aged children are more likely to have symptoms parents can observe, such as poor appetite, sleepiness, and respiratory symptoms (eg, a cough). School-aged children are more likely to have neurologic symptoms, eg, trouble focusing, trouble sleeping, or feeling lightheaded. They may also have back or neck pain, headache, stomach pain, or vomiting. Sometimes, they have behavioral changes. Adolescents are more likely to have a change or loss in smell or taste, pain, fatigue-related symptoms, trouble with memory, and lightheadedness. Postexertional malaise (PEM) has been reported in children and adults with long COVID. PEM is a flare of symptoms and/or the appearance of new symptoms even after minimal exertion, including physical activity, mental exertion, and sensory overload.

Long COVID is a complex, heterogeneous syndrome affecting over four hundred million people globally. There are few recommendations, and no formal training exists for medical professionals to assist with clinical evaluation and management of patients with Long COVID. More research into the pathology, cellular, and molecular mechanisms of Long COVID, and treatments is needed.

This study, using a 3-round modified Delphi consensus methodology, established conditions for diagnosis of different subgroups within the Long COVID umbrella. Clear consensus was reached that the impacts of COVID-19 infection on children should be a research priority, and additionally on the need to determine the effects of Long COVID on societies and economies.

The consensus on COVID and Long COVID is that it affects the nervous system and other organs and is not likely to be observed with initial symptoms. The authors note that biomarkers are critically needed to address these issues.

This 3 round modified Delphi consensus survey was distributed to 179 healthcare professionals, researchers, and persons with lived experience of Long COVID in 28 countries. The survey resulted in 187 comprehensive statements reaching consensus with the strongest areas being diagnosis and clinical assessment, and general research. We establish conditions for diagnosis of different subgroups within the Long COVID umbrella.

Clear consensus was reached that the impacts of COVID-19 infection on children should be a research priority, and additionally on the need to determine the effects of Long COVID on societies and economies.
The consensus on COVID and Long COVID is that it affects the nervous system and other organs and is not likely to be observed with initial symptoms. We note, biomarkers are critically needed to address these issues.

This work forms initial guidance to address the spectrum of Long COVID as a disease and reinforces the need for translational research and large-scale treatment trials for treatment protocols.

In this large cohort study including pediatric patients with and without COVID-19, infection was associated with a higher incidence of new-onset chronic kidney disease and worsening kidney function, especially among those with preexisting kidney disease or acute kidney injury.

These findings underscore the need for vigilant monitoring and management of kidney health in pediatric patients following SARS-CoV-2 infection.

The study authors state that in the adult population, there has been substantial interest in the potential efficacy of nutritional supplements. Regrettably, information regarding the use of such supplements in the pediatric population is currently lacking.

This proof-of-concept study revealed that MEP and lactoferrin, when administered three months after initial infection in patients with a new diagnosis of long covid, may have a positive impact on improving Long COVID symptoms in children during follow-up evaluations.

This positive trend toward reducing Post-COVID Condition (PCC) exhibited by MEP and lactoferrin suggested a potential benefit worthy of exploration in future randomized controlled trials.

Long COVID in children and young people (CYP) has posed significant challenges for health systems worldwide. Despite its impact on well-being and development, policies addressing the needs of CYP remain underdeveloped.

Analysis of policy documents and social media discourse highlighted gaps in accountability, inclusiveness, and transparency in policy development. Social media data reflected significant public dissatisfaction, primarily critiquing government accountability (90% of posts) and delayed policy responsiveness (29% of posts). Key ethical challenges included limited CYP representation and unequal access to services.

Recommendations include improving transparency, incorporating CYP perspectives in policymaking, and ensuring equitable access to care. These findings provide a foundation for ethically sound and inclusive policies addressing Long COVID in CYP.

The risk of cardiovascular outcomes following SARS-CoV-2 infection has been reported in adults, but evidence in children and adolescents is limited.
This paper assessed the risk of a multitude of cardiac signs, symptoms, and conditions 28-179 days after infection, with outcomes stratified by the presence of congenital heart defects (CHDs), using electronic health records data from 19 children’s hospitals and health institutions from the United States within the RECOVER consortium between March 2020 and September 2023. The cohort included 297,920 SARS-CoV-2-positive individuals and 915,402 SARS-CoV-2-negative controls.

The authors show that children and adolescents with prior SARS-CoV-2 infection are at a statistically significant increased risk of various cardiovascular outcomes, including hypertension, ventricular arrhythmias, myocarditis, heart failure, cardiomyopathy, cardiac arrest, thromboembolism, chest pain, and palpitations, compared to uninfected controls. These findings were consistent among patients with and without CHDs.

Awareness of the heightened risk of cardiovascular disorders after SARS-CoV-2 infection can lead to timely referrals, diagnostic evaluations, and management to mitigate long-term cardiovascular complications in children and adolescents.

Pregnancy alters immune responses and clinical manifestations of COVID-19, but its impact on Long COVID remains uncertain. This study investigated Long COVID risk in individuals with SARS-CoV-2 infection during pregnancy compared to reproductive-age females infected outside of pregnancy.

At 180 days after infection, estimated Long COVID risks for those infected during pregnancy were 16.47 per 100 persons (using the PCORnet computational phenotype (CP) model) and 4.37 per 100 persons (using the N3C CP model).

The observed risk factors for Long COVID included Black race/ethnicity, advanced maternal age, first- and second-trimester infection, obesity, and comorbid conditions.

While the findings suggest a high incidence of Long COVID among pregnant individuals, their risk was lower than that of matched non-pregnant females.

This review article states that:

In short, PAFs (Portable Air Filters) are an important tool to help reduce the risk of transmission of airborne infectious diseases.

Moreover, PAFs are relatively simple to use, and there is a variety of high-quality guidance available for their deployment.

We share this science here with the expectation that, going forward, public health authorities will position PAFs appropriately in infection prevention and control plans for both health care and community settings.

Study Highlights:

Cognitive engagement induced distinct prefrontal haemodynamic patterns post COVID-19.

40% of the undergraduate students reported brain fog due to COVID-19.

37 % of the undergraduates exhibited impaired cognition up to 17 months post-infection.

Brain fog appeared to affect the distinct prefrontal haemodynamic patterns.

This study proposes that the co-detection of PIV3 and SARS-CoV-2, as well as HRV and RSV, may play a more important role in the era of omicron than previous variants, such as delta, regarding clinical manifestations.

A growing body of evidence shows that SARS-CoV-2 can persist for months or years following COVID-19 in a subset of individuals, with this reservoir potentially driving long-COVID symptoms or sequelae. There is, therefore, an urgent need for clinical trials targeting persistent SARS-CoV-2, and several trials of antivirals or monoclonal antibodies for long COVID are underway.

However, because mechanisms of SARS-CoV-2 persistence are not yet fully understood, such studies require important considerations related to the mechanism of action of candidate therapeutics, participant selection, duration of treatment, standardisation of reservoir-associated biomarkers and measurables, optimal outcome assessments, and potential combination approaches. In addition, patient subgroups might respond to some interventions or combinations of interventions, making post-hoc analyses crucial.

Here, the authors outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Their recommendations are informed by knowledge gained from trials targeting the HIV reservoir, hepatitis C, and other RNA viruses, as well as precision oncology, which share many of the same hurdles facing long-COVID trials.

Children and adolescents with documented SARS-CoV-2 infection faced a 25% higher risk of newly diagnosed GI tract symptoms and disorders during the postacute phase compared with those without documented SARS-CoV-2 infection (incidence, 8.64% vs 6.85%).

The final study sample included 54 participants (27 participants with PCC and 27 matched controls). Twenty-one participants had cardiopulmonary symptoms. Participants with PCC had lower regional ventilation and quantified perfusion. Participants with PCC and cardiopulmonary symptoms had lower FVL-CMs and higher ventilation defect and perfusion defect percentage compared with matched control participants.

In participants with PCC, greater lung perfusion correlated with increased chronic fatigue severity and higher ventilation-perfusion mismatch correlated with increased heart rate.

The authors conclude that Free-breathing phase-resolved functional lung MRI–derived parameters helped identify a distinct phenotype of lung perfusion in children and adolescents with PCC and were correlated with heart rate and chronic fatigue severity.

​

One lingering effect of the COVID-19 pandemic created by SARS-CoV-2 is the emergence of Long COVID (LC), characterized by enduring neurological sequelae affecting a significant portion of survivors.

This review provides a thorough analysis of these neurological disruptions with respect to cognitive dysfunction, which broadly manifest as chronic insomnia, fatigue, mood dysregulation, and cognitive impairments with respect to cognitive dysfunction.

Furthermore, the authors characterize how diagnostic tools such as PET, MRI, EEG, and ultrasonography provide critical insight into subtle neurological anomalies that may mechanistically explain the Long COVID disease phenotype. They explore the mechanistic hypotheses of these neurological changes, which describe CNS invasion, neuroinflammation, blood-brain barrier disruption, and gut-brain axis dysregulation, along with the novel vascular disruption hypothesis that highlights endothelial dysfunction and hypoperfusion as a core underlying mechanism.

They lastly evaluate the clinical treatment landscape, scrutinizing the efficacy of various therapeutic strategies ranging from antivirals to anti-inflammatory agents in mitigating the multifaceted symptoms of LC.

The authors concluded that their findings demonstrate a significant increase in the incidence of POTS following the COVID-19 pandemic, suggesting a potential association between COVID-19 infection and the development of post-viral POTS. Future research should explore the underlying mechanisms and treatment strategies for POTS in the context of post-COVID recovery.

The authors identified 45 203 children younger than 18 years old in whom SARS-CoV-2 either caused or contributed to hospitalization, excluding those admitted with “incidental” infection.

There were 45 920 SARS-CoV-2–related hospitalizations in children: 75.9% attributable to COVID-19; 4.0% attributable to PIMS-TS; 18.1% with SARS-CoV-2 as contributor to admission; and 1.9% acquired nosocomial SARS-CoV-2 infection.

The authors conclude that infants are now the pediatric age group most affected by SARS-CoV-2, at least partially because they have the least immunity to the virus, and are most vulnerable to respiratory illnesses.

The authors retrospectively studied nine confirmed pediatric cases of COVID-19 complicated with CNS injury who were admitted to the pediatric intensive care unit of the Affiliated Hospital of Jining University from December 1, 2022 to January 12, 2023. Of the nine patients, seven were male. Five children were aged ≥ 10 years, and the others were 1–2 years old.

All children had fever, eight had convulsions, seven had progressed to multiple organ failure, and all suffered varying degrees of coma. Most of the children had elevated interleukin-6 (100%), lactic acid (100%), alanine transaminase (87.5%), aspartate transaminase (87.5%), creatine kinase MB (87.5%), and lactate dehydrogenase (85.7%) levels. Four children had cerebrospinal fluid proteinnacell separation. The cranial imaging results of five children were abnormal. One child had lost his vital signs when admitted to hospital, and the remaining eight received hormonal shock, human immunoglobulin transfusion, antinainfection, cranial pressure reduction, and tracheal intubation, among others, during hospitalization. Ultimately, eight children died, and the remaining child has serious neurological sequelae and is undergoing rehabilitation.

Conclusions Severe CNS injury caused by COVID-19 has an acute onset, rapid progression, high disability rate, and high fatality rate. A low cerebrospinal fluid protein level may be a protective factor for children with severe nervous system injury caused by COVID-19.

In this cohort study of 614 children with daily diary information on common infection load in early life, the overall infection burden in early life was associated with increased risks of moderate to severe infections and antibiotic treatments later in childhood.

IVIG has shown efficacy in over 100 disorders, spanning hematologic, inflammatory, autoimmune, and infectious diseases. IVIG acts by neutralizing cytokines/autoantibodies, saturating FcRNs, inhibting complement, and overall immunoregulation.

In Post Acute Sequalae of Covid-19 (PASC), while research is still in early stages, IVIG has been shown to alleviate persistent symptoms in small patient cohorts. Furthermore, IVIG has shown benefits in (ME/CFS), though studies have yielded mixed results.

It is important to note that IVIG can be associated with several potential adverse effects and in addition, the high cost of IVIG can be a deterrent for payers and patients.

The authors suggest that future PASC studies could focus on patient subgroups, symptom clusters, and optimal IVIG dosing and timing.

Over a 3-year period, 2 855 704 pediatric patients with symptomatic SARS-CoV-2 infection were registered in Brazil. 2.1% were hospitalized, 0.48% were admitted to intensive care, 0.17% received mechanical ventilation.
A total of 4740 (0.17%) patients had fatal outcomes. The case fatality rate increased to 7.9% among patients who required hospitalization; 2102 (44.3%) patients who died did not receive advanced critical support. Notably, 2 or 3 doses of the vaccine provided strong protection against death.
The following adjusted covariates were significantly associated with increased odds of death: age (0-4 and 11-17 years), ethnicity (Brown and Indigenous), region (Northeast or North), dyspnea, nosocomial infection, and comorbidities. Conversely, living in the South or Central-West regions, admission in the later period of the pandemic, and receiving a vaccine were all associated with protection against death.
In conclusion, the authors state their "findings suggest that a complex interplay between individual factors and social inequities has shaped the impact of COVID-19 on Brazilian children and adolescents"

Pediatric Long COVID patients have a well distinct blood protein signature marked by increased ongoing general and endothelial inflammation, similarly as happens in adults.

Impact
- Pediatric Long COVID has a distinct blood protein signature marked by increased ongoing general and endothelial inflammation.
- This is the first study studying and documenting proinflammatory profile in blood samples of children with long COVID.
- Long COVID was characterized by higher expression of the proinflammatory and pro-angiogenetic set of chemokines CXCL11, CXCL1, CXCL5, CXCL6, CXCL8, TNFSF11, OSM, STAMBP1a.
- A proteomic profile was able to identify Long COVID with an accuracy of 0.93, specificity of 0.86 and sensitivity of 0.97.
- These findings may inform development of future diagnostic tests.

SARS-CoV-2 infection during pregnancy can adversely affect maternal and neonatal health, although risks vary depending on the variant of concern (VOC).

Using data from the CRONOS registry, the authors compared pregnancy outcomes according VOC and vaccination status and found that vaccination during pregnancy reduced preterm birth rates compared with unvaccinated or vaccinated women with Omicron infection, without increasing severe neonatal outcomes.

Given the risks associated with preterm birth, the study consistently supports vaccination recommendations for women planning pregnancy.

"Results of this cohort study suggest that although children and young adults with MIS-C can have severe disease during the acute phase, most recovered quickly and had a reassuring midterm prognosis.
90%"
Very sadly, this study does show that 3 of these youngsters died during hospitalisation and 5% were still not yet 90% recovered at the six month point.

These results indicate that vaccination prior to SARS-CoV-2 infection does not affect the neurologic manifestations of long COVID in either PNP (post-hospitalisation neuro-PASC patients) or NNP (non-hospitalised neuro-PASC) patients .
Minor differences in neurologic symptoms between pre-vaccination infection and breakthrough infection groups may be caused by SARS-CoV-2 strains evolution. Patients developing Neuro-PASC after breakthrough infection have a higher burden of comorbidities, highlighting different risk factors warranting targeted management.

This study investigated the impact of both SARS-CoV-2 infections and vaccinations on the incidence of acute and prolonged symptoms in real-world conditions during the transition from the pandemic to the endemic phase.
Nearly all participants developed SARS-CoV-2 antibodies in this longitudinal study through either vaccination or infection during the Omicron wave.
About 7% of participants suffered from PCS symptoms, predominately fatigue and exhaustion, for more than three months and up to four years.
Furthermore, participants who received vaccinations against SARS-CoV-2 reported a lower frequency of acute infections during follow-up.

Among children below 5 years of age in the USA, more than 7000 children were hospitalized, and an estimated 700 children died due to COVID-19 as of April 2023. COVID-19 is ranked among the leading causes of mortality for children, and deaths due to COVID-19 are higher than for other vaccine-preventable diseases among children below 5 years of age.

Vaccinating children against COVID-19 is the primary way to reduce the disease burden in this age group. Data from the clinical trials showed that these vaccines are safe and efficacious, and recent observational studies have found that the vaccines effectively reduce the risk of symptomatic COVID-19 infection, hospitalization, long COVID and multisystem inflammatory syndrome in children.

This study found that nearly half (45.6 %) of pregnant or postpartum women were hesitant to vaccinate their child against COVID-19. and that the women who were hesitant about getting children <5 vaccinated cited the following reasons for hesitancy: concerns about the vaccine, lack of evidence on vaccine safety, and the COVID-19 vaccine is not necessary for children.

The authors conclude that public health messages to promote the COVID-19 vaccine for young children should focus on the risks and consequences of the disease and share data on the effectiveness of the vaccine in preventing severe COVID-19-related outcomes.

This study found that 7.2% of CYP consistently meet the ‘Long COVID’ research definition at 3-, 6-, 12- and 24-months post infection

25-30% of those unwell at 12 weeks still had Long Covid 2 years later. The reinfected group had more symptoms than the other two positive groups and thus had a higher prevalence of PCC (30%vs.~25%)

Sammie McFarland issued a comment on the study
"Two years is a long time in the life of a child. While the study reassures us that most participants recovered within this period, the 30% of children and young people still affected highlights that Long Covid remains a significant childhood illness and a pressing concern.
This underscores the urgent need for effective treatments to ease the ongoing burden of this illness"

Recent evidence demonstrates an increase in negative maternal and neonatal outcomes in cases of SARS-CoV-2 infection, such as greater severity of the disease, need for mechanical ventilation and longer hospitalization in intensive care units.

Furthermore, there are obstetric and neonatal impacts associated with COVID-19 infection during pregnancy, such as premature rupture of ovular membranosa, prematurity, fetal distress, increased number of cesarean sections, tachypnea, neonatal sepsis and death maternal.

COVID-19 infection can also cause damage to the placenta. Placental, signs of maternal-fetal vascular malperfusion, zones of avascular villi, villous thrombi and infarction and villous edema can be observed.

In addition to histiocytic intervillositis, deposition of perivillous or subchorionic fibrin, trophoblastic necrosis and increased incidence chorangiosis. These changes are mainly due to cellular reactions caused by the death of the virus, the action of anti-SARS-CoV antibodies, the local inflammatory process and syncytiotrophoblastic ischemia, without necessarily having a placental infection.

The most common categories of symptoms identified as raising suspicion for long COVID in children included cardiopulmonary symptoms, selected by 119 (99%) of pediatric providers, and neurocognitive symptoms, selected by 118 (98%) of providers.
However, there was more ambiguity on the primary feature of long COVID, with providers selecting a range of key symptoms.
Of all physical exam findings, postural orthostatic tachycardia, was most suggestive of long COVID [identified by 49 (41%) of pediatric providers], whereas one-third of providers reported no specific identifiable exam finding.

There is growing understanding that Social Determinants of Health (SDH) impact on the outcomes of different pediatric conditions.

The study authors found that the Score of Social Disadvantage was associated with shock, respiratory support, transfusion, but not death.

They conclude that among a large cohort of Latin American children with MIS-C, SDH negatively affect outcomes.

These findings reinforce the need for better investigation of the role of SDH in MIS-C and other inflammatory conditions and may guide public health interventions.

The study results highlight the relative importance of household and family transmission in the spread of SARS-CoV-2 compared to school settings.

The authors state that it is worth noting, however, that even small increases in school-related infection probabilities can trigger large-scale outbreaks due to the dense network of interactions in these settings.

The study found that the largest differences in transmission probabilities were due to unobserved individual (60%) and school-level (35%) factors.

Based on the Bradford Hill criteria and modelling, HAdv alone is unlikely to be the cause of the recent increase in hepatitis in children.

The causal link between SARS-CoV-2, and to a lesser degree AAV-2, appears substantially stronger but remains unproven.

Hepatitis is a known complication of multisystem inflammatory syndrome in children following COVID-19, and SARS-CoV-2 has been linked to increased susceptibility to infection post-COVID-19, which may suggest complex causal pathways including a possible interaction with AAV-2 infection/reactivation in hosts that are genetically susceptible or sensitised to infection.

Maternal COVID-19 infection increases the incidence of neurodevelopmental disorders (NDDs) in offspring, although the underlying mechanisms have not been elucidated.

This study demonstrated that COVID-19 infection during pregnancy disrupted the balance of maternal and fetal immune environments, driving alterations in astrocytes, endothelial cells, and excitatory neurons. The high risk score in CD4 proliferating T cell level served as an indicator for increased risk of offspring NDDs. 10 drugs were identified as potential therapeutic candidates.

Our findings support a model where the maternal COVID-19 infection changed the levels of CD4 proliferating T cells, leading to the alterations of astrocytes, endothelial cells, and excitatory neurons in offspring, contributing to the increased risk of NDDs in these individuals.

Considering the observations of viral reactivation in COVID-19, the experienced role of neutrophils during the acute phase, and their disturbed activity’s pathogenic role in other diseases, the authors hypothesized an ongoing disruption in their functioning during COVID-19’s prolonged phase.

Neutrophilic granulocyte dysfunction was found in children with Long Covid, with decreased superoxide-producing activity and phagocytosis compared to controls.

The number of complaints of children with LCS correlated significantly with altered neutrophil effector functions.

The authors state that "By detecting neutrophilic granulocyte dysfunction in children with LCS, we shed light on a previously overlooked pathophysiological component of the condition"

Estimating the impact and cost effectiveness of vaccinating UK adults ≥65 years and eligible persons 6 months to 64 years of age over a 1-year time horizon.
Vaccination of the eligible population would contribute to significant reductions in hospitalizations, deaths, and long COVID in the UK in the 2024–2025 season. Expanding the target population continues to be cost-effective.
Use of the Moderna Autumn 2024 Campaign is predicted to reduce SARS-CoV-2 infections and associated outcomes in a cost-effective manner and will contribute to a more resilient healthcare system in the UK.

Long Covid Kids is concerned that vaccine impact and cost effectiveness studies continue not to take the disability caused by Long Covid in to account.

Infection with SARS-Cov-2 in pregnancy is associated with increased maternal morbidity and mortality. Associations have also been reported with placental complications, including stillbirth and pre-eclampsia.
The authors of this study sought to evaluate whether there was a change in the incidence of congenital heart defects among live births in the USA during the Covid-19 pandemic.

The incidence of cyanotic congenital heart defects was significantly higher during the post interruption period compared with the pre interruption period. The reasons underlying this finding are uncertain, but this raises the possibility that infection with SARS-Cov-2 could be associated with foetal cyanotic cardiac abnormalities

These results warrant further research in to the association between infection with Covid-19 disease and foetal cyanotic congenital heart defects.

This study recognises that some children may suffer consequences of Covid-19 infections and it looks at Long Covid and multisystem inflammatory syndrome in children (MIS-C).

Estimated from population-based studies, 1.3% of US children have been reported to have Long Covid, a broad spectrum of symptoms. They recognise that, in addition to new or ongoing symptoms, SARS-CoV-2 infection can increase the risk of newly diagnosed conditions after acute illness. There is a 200% increased risk of myocarditis and a 20% increased risk of type 1 diabetes compared with those who did not have COVID-19.

They state that MIS-C is generally considered unique from Long Covid. The clinical presentation of children with MIS-C is often initially severe, with approximately half requiring admission to the intensive care unit often because of cardiovascular involvement with shock or decreased cardiac function visualized on echocardiography and that, although the occurrence of these conditions has decreased over time, they can still occur, and recognition of symptoms and prompt diagnosis is imperative for early intervention.

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition has been reported.

We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, “burdenMC,” which identified an enrichment for rare predicted-deleterious variants in BTNL8. BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis.

Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Eight variants were identified in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells.

These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2.

In this pre-print, the authors conclude that their study suggests that Long Covid is associated with persistent liver damage and coagulopathy, highlighting the need to incorporate liver injury into treatment strategies to reduce potential risks.
The findings highlight that Long Covid involves multiple organ systems, which may lead to serious complications if not closely monitored.

Compared with the control group, the COVID group in the post-COVID condition had more severe symptoms of inattention, hyperactivity-impulsivity, opposition, a wide range of emotional and behavioral problems, and poor school functions, school attitude, social interaction, school behavioral problems, and interaction problems with their parents.
Compared with the pre-COVID condition, the COVID group had greater severity of inattention, somatic complaints, thought problems, internalizing problems, poor school functions, and interaction problems with their parents in the post-COVID condition.
Conclusions:
The present study identified a significant link between SARS-CoV-2 infection and various post-COVID mental health sequelae in children, including behavioral/emotional and social adjustment challenges. Our results underline the importance of raising awareness about ongoing post-COVID mental health concerns in children.

Long COVID is a major public health consequence of COVID-19 and is characterized by multiple neurological and neuropsychatric symptoms. SARS-CoV-2 antigens are found in the circulation of Long COVID patients, have been detected in post-mortem brain of COVID patients, and exhibit neuroinflammatory properties. Considering recent observations of chronic neuroinflammation in Long COVID patients, the present study explores the idea that antigens derived from SARS-CoV-2 might produce a long-term priming or sensitization of neuroinflammatory processes, thereby potentiating the magnitude and/or duration of the neuroinflammatory response to future inflammatory insults.

In this cohort study of 613 602 pediatric patients aged 10 to 19 years those with a COVID-19 diagnosis were significantly more likely to be diagnosed with T2D during the subsequent 6 months than propensity score–matched children who had other respiratory infections.
The authors note that further study is required to determine whether diabetes persists or reverses later in life and they conclude that understanding the role that SARS-CoV-2 plays in pediatric T2D incidence will add an important component to consideration of the risks and benefits of preventing SARS-CoV-2 infection in children.

The authors conclude that Long COVID affects multiple systems, posing a particular challenge for PCOS patients who may experience aggravated symptoms and complicated management.

Current evidence indicates that COVID-19 and its sequelae negatively impact reproductive health, endocrine function, inflammation, metabolism, cardiorespiratory health, body composition, lifestyle, and mental health in patients with PCOS.

These mechanisms are multifactorial and include inflammation, lifestyle changes, and comorbidities. Given the lack of effective therapies for PCOS post-COVID-19, a comprehensive multidisciplinary approach is crucial for its management.

Future research and clinical trials are needed to evaluate treatment and prevention strategies, emphasizing the importance of personalized care and risk assessment in patients with PCOS and COVID-19.

This is the longest follow-up study of children with SARS-CoV-2 infection, showing a significant and long-lasting burden of Long Covid in the pediatric population.
As the authors state, their "findings highlight the urgent need of investing in pediatric Long Covid in order to find effective diagnostic and therapeutic approaches, as well can inform preventive strategies in case of future pandemics"

This observational study involved 56 healthy children, aged between 7 and 18 years, who were diagnosed with COVID-19 infection from July 2021 to February 2023.

Post-COVID-19 symptoms were identified in 25%, with fatigue, cough, and dyspnea being common symptoms (28%–35%). A significant correlation was found between post COVID-19 symptoms and pneumonia. Abnormal pulmonary function was identified in 17.8% with obstructive impairment being the most common.

The authors conclude that prolonged respiratory symptoms and abnormal pulmonary function following COVID-19 infection are not uncommon in children. The post-COVID-19 symptoms are possibly associated with COVID-19 pneumonia.

"Here we review and discuss the content on different aspects of long COVID, including its pathophysiology and the existing evidence of a potential relationship between such a condition and gut candidiasis"

"More research is needed to address the specifics of a possible relationship between gut candidiasis and long coronavirus disease, in order to provide more robust knowledge on the topic, and consequently more appropriate management and treatment for affected patients. This, in turn, could lead to greater understanding and learning about the subject among all related healthcare professionals, with the potential to achieve better outcomes and improved quality of life and quality of care for the population"

Bistagnino F, Pizzi D, Mantovani F, Antonino JR, Tovani-Palone MR

Mucormycosis, popularly known as the black fungus, has become a worldwide concern in the continuing COVID-19 pandemic
Mucormycosis in people having COVID-19 infection is reported globally, yet proper treatment of this coinfection is not available and unsatisfactory.

This review highlights the role of nanomaterials and their potential to combat Murcomycosis. It discusses key areas for improvement, and limitations, along with their possible solution and states that "Future research in this area holds a high hope to develop nano-based effective therapeutics against this coinfection".

In this cohort study of 172 136 children and young adults, elevated BMI was associated with significantly higher risk of PASC. Compared with peers with a healthy BMI, there was a 25.4% increased risk of PASC among those with obesity and a 42.1% increased risk of PASC among those with severe obesity.

These findings suggest that overweight and obesity are important risk factors for pediatric PASC, highlighting the need for targeted care to prevent chronic conditions in at-risk children and young adults who are infected with SARS-CoV-2.

This study of 129 patients One-hundred and twenty-nine patients used fatigue, neuropsychological, and subjective cognitive complaints assessments as well as structural and functional MRIs. Functional connectivity, white matter diffusivity and grey matter volume were evaluated.

Fatigue was present in 86 % of patients studied, and was highly correlated to subjective cognitive complaints. Fatigue was associated with structural and functional connectivity mostly in frontal areas but also temporal, and cerebellar areas, showing mental fatigue different pattern of functional connectivity correlates compared to physical fatigue.

White matter diffusivity correlates were similar in fatigue and subjective cognitive complaints, located in the forceps minor, anterior corona radiata and anterior cingulum. Findings confirm that fatigue in post-COVID syndrome is related to cerebral connectivity patterns, evidencing its brain substrates. Moreover, results highlight the relationship between fatigue and subjective cognitive complaints.

These findings point out the relevance of the multidisciplinary assessment of post-COVID syndrome patients with subjective cognitive complaints, in order to unravel the symptomatology beneath the patient's complaints.

In this cohort study of 172 136 children and young adults, elevated BMI was associated with significantly higher risk of PASC. Compared with peers with a healthy BMI, there was a 25.4% increased risk of PASC among those with obesity and a 42.1% increased risk of PASC among those with severe obesity.

These findings suggest that being overweight and obesity are important risk factors for pediatric PASC, highlighting the need for targeted care to prevent chronic conditions in at-risk children and young adults who are infected with SARS-CoV-2.

During short-term (4–12 weeks) follow-up, the older age of patients significantly increased the risk of long COVID symptoms in children after MIS-C. Patients who report symptoms up to 12 weeks after MIS-C continued to present with symptoms beyond 24 weeks, which could help plan care after hospital discharge.
During long-term (over 24 weeks) follow-up, the QoL after MIS-C seems to be non-inferior to the overall paediatric population.

Long COVID is a chronic and often disabling illness with long-term consequences. The authors recognise that children also suffer substantial morbidity from long COVID, with a recent Pediatrics study estimating that up to 5.8 million children in the US are affected by long COVID

They state that although progress has been made in the clinical characterization of long COVID, no approved treatments exist and disconnects between patients and researchers threaten to hinder future progress.

The Patient-Led Research Collaborative (PLRC) is an international research and advocacy organization operated by people with long COVID. Scientists, researchers, healthcare workers, community organizers, and other professionals who have long COVID or an associated condition and/or are caregivers for someone with the condition. They call for the need to incorporate patients as active collaborators in long COVID research, and state that this can bridge the gap and accelerate progress toward treatments and cures.

COVID-19 affects the thyroid gland multifacetedly and includes direct viral invasion, immune-mediated damage, and hypothalamic-pituitary-thyroid axis disruption.

Approximately 15% of COVID-19 patients experience thyroid dysfunction, which can present as thyrotoxicosis, hypothyroidism, or non-thyroidal illness syndrome (NTI). Noteworthy findings include inflammatory thyroiditis.

Long-term effects, including those observed in children, include persistent hypothyroidism and exacerbated pre-existing thyroid-autoimmune conditions.

Management of thyroid disorders in COVID-19 patients requires consideration: anti-thyroid drug therapy used to treat hyperthyroidism in COVID-19 patients may need adjustment to prevent immunosuppression. Radioactive iodine alternatives and interleukin-6 receptor antagonists could offer potential benefits and should be further explored.

Gastrointestinal (GI) complications are significant manifestations of COVID-19 and are increasingly being recognized.

The study highlights a broad range of GI complications following COVID-19 infection, including inflammatory conditions, such as ulcerative colitis (UC), acute pancreatitis, and multisystem inflammatory syndrome in children (MIS-C). Other GI complications were reported such as vascular disorders, including diverse thrombotic events and structural abnormalities, which ranged from bowel perforations to adhesions. Additionally, undiagnosed conditions like nausea and abdominal pain were prevalent across different studies involving 561 patients.

The findings emphasize the substantial impact of COVID-19 on the GI tract. Ongoing research and monitoring are crucial to understanding the long-term effects and developing effective management strategies for these complications.

This study reveals that children with Long COVID symptoms had notably higher odds of ED visits, with chest pain, fluid imbalances, and generalized pain being most closely linked to such visits.

This study highlights the burden of Long COVID on ED providers and underscores the importance of improved guidance for managing Long COVID symptoms in children.

Although rare, hypophysitis related to COVID-19 is documented in the literature

Longer-term follow-up of these patients is needed to better understand the potential lasting impact on pituitary function and radiological improvement.

Future research should also explore the presence of anti-pituitary antibodies and the other possible pathophysiological mechanisms potentially involved in these cases.

The quality of the classroom environment, including ventilation, air quality and thermal conditions, has an important impact on children’s health and academic achievement
Results of this study indicate the addition of HEPA filters was predicted to reduce PM2.5 by 40–60 % and viral RNA by 30–50 % depending on the classroom design and window opening behaviour. The energy cost of running HEPA filters is likely to be only 1 %–2 % of the classroom heating costs. In scenarios when HEPA filters were on and window opening was reduced (to account for the additional clean air delivery rate of the filters), the heating cost was predicted to be reduced by as much as − 13 %, and these maximum reductions grew to − 46 % in wintertime simulations. In these scenarios the HEPA filters result in a notable reduction in PM2.5 and viral RNA, but the CO2 concentration is significantly higher.

After a long period of stability in the IR of T1DM in children younger than 15 years of age in Biscay, Spain, an increase in recent years has been reported, which is consistent with the SARS-CoV2 pandemic, with the largest increase being reported in the 5-to 9-year-old age group.

There is potential for SARS-CoV-2 to induce autoimmune responses, exacerbate existing endocrine conditions, and trigger new-onset disorders.

Understanding these interactions is crucial for developing treatment strategies that address not only the respiratory symptoms of COVID-19 but also its endocrine complications.

The review emphasizes the need for further research to elucidate the long-term effects of SARS-CoV-2 on endocrine health.

This, case-controlled, study of mildly infected youth showed persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition.

The left hippocampus showed a significant decrease in Volumetricdelta between groups. The reduced ECdelta in the left amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory.

These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.

We enrolled 298 participants. Symptomatic COVID-19 infection after vaccination occurred in half of the participants, although only 2 required hospitalization. Anti-tumor necrosis factor alpha was associated with higher likelihood of symptomatic COVID-19 infection.

SARS-CoV-2 vaccination provides lasting serologic response and protection against severe COVID-19 for most children with IBD, despite the use of lower vaccine doses in younger children and wide-ranging classes of immunosuppressive therapies.

Long COVID has been extensively reported both in adults and children, particularly adolescents, and can follow even mild to asymptomatic infections or reinfections.

A growing body of literature has documented that several biological abnormalities are evident in patients with Long COVID compared with healthy controls, including events associated with thromboinflammation, persistent immune activation and imbalance. However, these studies have been limited to adults only, and so far, no studies have attempted to provide a deep cytokine profile of children with a previous SARS-CoV-2 infection.

Here, the authors provide preliminary evidence that, also in children, Long coronavirus disease (COVID) may be characterized by a proinflammatory signature. Ten Long COVID patients, 7 convalescent subjects after COVID infection and 4 healthy controls were enrolled.

When adjusted for sex, children with long COVID had statistically significant differences in the levels of Flt3L, CD5, uPA, CCL23, CD40 and TGFα. When adjusted for age, CCL23 levels remained statistically significant.

The authors illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C/PIMS) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls.
They go on to explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls.
Their study shows that that neutrophil activation and apoptosis are prominent in MIS-C/PIMS and that this is partially shared with bacterial infection.
They show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. I
In contrast, they show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression.
Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children.

COVID-19 has been shown to impair cardiovascular function, and further studies have proven that this effect can be long-term on several cardiovascular biomarkers.

The study showed that patients who had survived COVID-19 had significantly higher levels of fetuin-A compared to healthy controls. Additionally, it was found that patients with high blood pressure had increased levels of fetuin-A compared to those without high blood pressure.

These results suggest that COVID-19 may alter the usual relationship between blood pressure and cardiovascular biomarkers. Further studies are needed to elucidate the underlying mechanisms, which will help develop effective clinical guidelines for managing cardiovascular health in COVID-19 survivors.

A total of 840 women with menstrual pain were studied. 84.2% had a COVID-19 infection, 123 did not (14.5%).

Conclusion: Subjects with SCE had a twofold increased risk of LC (in comparison to subjects with nonconfirmed endometriosis menstrual pain). In patients with SCE concomitant diagnosis of depression or anxiety disorder further twice-fold increased risk of LC.

Further studies are needed to establish if it is possible to reduce LC risk by improving the treatment of those secondary diagnoses and whether the type of endometriosis treatment can reduce LC occurrence.

The coronavirus disease 2019 (COVID-19) pandemic increases the risk of adverse fetal outcomes during pregnancy. Current research on COVID-19 remains insufficient, particularly regarding its impact on pregnancy. Notably, a substantial amount of data now exists that reveals how infection can affect pregnancy outcomes

This study aimed to investigate the potential impact of COVID-19 pandemic on oxygen levels at the maternal–fetal interface and overall, it suggests that SARS-CoV-2 infection during the first trimester leads to severe hypoxia and aberrant cell metabolism at the maternal–fetal interface which gradually resolves as pregnancy progresses.

Nevertheless, these abnormal changes may have long-term implications for maternal–fetal interface development.

While most children follow a milder course of infection with symptoms such as fever, congestion, and typical cold symptoms, some children present with more significant symptoms including, respiratory distress and multifocal pneumonia requiring supplemental oxygen and/or positive pressure ventilation. In severe pediatric cases, SARS-CoV-2 infection has led to multiorgan failure or acute respiratory distress syndrome (ARDS)
Some children began to develop severe illnesses with high fevers, severe abdominal pain, diffuse rash, and, in many instances, cardiovascular complications, including ventricular failure, coronary dilations or aneurysms, or cardiogenic shock, resembling features of Kawasaki’s disease, although in older children and adolescents. This Kawasaki like illness is now termed Multisystem Inflammatory Syndrome in Children (MIS-C).
Across the waves of the pandemic, the severity of hospitalized children ages 5 to 18 years has decreased, and fewer hospitalized children have required ICU admission, ventilatory support, or supplemental oxygen. However, the same reduction in severity has not been seen in hospitalized children less than 5 years of age.

Preprint

Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions.

The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue.

Exhaled breath specimens were collected from COVID-19 patients. RTq-PCR was used to show that numbers of exhaled SARS-CoV-2 RNA copies during COVID-19 infection do not decrease significantly until day 8 from symptom-onset.
After day 8, there was a steep drop to levels nearing the limit of detection, persisting for up to 20 days. We further found that levels of exhaled viral RNA increased with self-rated symptom-severity, though individual variation was high. Levels of exhaled viral RNA did not differ across age, sex, time of day, vaccination status or viral variant.

In this study, two-thirds of the children developed long COVID symptoms, most frequently in the age 5-9 years group, and mostly fatigue (45.2%), decreased appetite (38.7%), and muscle aches (32.3%).

All patients with moderate to severe and more than half asymptomatic to mild COVID-19 developed long COVID.

The study concluded that most children had long COVID symptoms similar to adults despite being otherwise asymptomatic or having mild COVID-19.

In this retrospective cohort study, 59,339 children and adolescents with laboratory-confirmed COVID-19 in 2020 and 170,940 matched controls were followed until 2021-09-30 using German routine healthcare data.
The authors found a particular increase in the risk of inflammatory disorders in children.
Conditions of fatigue were considerably more frequent in the COVID-19 group. Malaise/exhaustion showed a slightly higher IRR in the COVID-19 group of adolescents aged 12–17 years compared to children aged 0–11 years. Considering ME/CFS our results show a significant risk increase following COVID-19 in adolescents. Such diagnoses were generally more frequent in adolescents than in young children. Despite a similar pattern of decreasing relative risk in both age groups, IRRs for these symptoms remained high after 12 months.
Some outcomes, especially cardiac symptoms, gastrointestinal symptoms, fatigue, and inflammatory disorders showed both initial excess risk of onset and prolonged persistence, meaning children and adolescents with a history of COVID-19 are affected more often by these symptoms and take longer to recover from them.

The mean age of the hospitalized children with COVID-19 was 79 ± 5.24 months old (6.5yrs), 57.4% of whom were boys. Also, 32.6% of the Covid group manifested long COVID symptoms.

The most prevalent symptoms included fatigue (54.3%), impaired attention or concentration (41.3%) and depression or anxiety symptoms (34.7%). Among the hospitalized children experiencing long-term COVID symptoms, 65.2% exhibited moderate disease severity.

A significant relationship was identified between disease severity and muscle and joint pain, as well as between the length of hospital stay and cough, weight loss, and symptoms of depression or anxiety.

The study found that as age increases and the history of tobacco smoke exposure rises, the likelihood of experiencing long-term COVID symptoms also increases.

This review explores the multifaceted long-term implications of COVID-19, with a particular focus on severe maternal COVID-19 infection, gut microbiome dysbiosis, and neurodevelopmental disorders in offspring. Severe COVID-19 infection has been associated with heightened immune system activation and gastrointestinal symptoms. It may also result in gut microbiome dysbiosis and a compromised intestinal mucosal barrier. Increased gut permeability facilitates the passage of inflammatory cytokines into the bloodstream, thereby influencing fetal development during pregnancy and potentially elevating the risk of neurodevelopmental disorders such as autism and schizophrenia.
The current review discusses the role of cytokine signaling molecules, microglia, and synaptic pruning, highlighting their potential involvement in the pathogenesis of neurodevelopmental disorders following maternal COVID-19 infection. Additionally, this review addresses the potential of probiotic interventions to mitigate gut dysbiosis and inflammatory responses associated with COVID-19.

The studies reviewed show that sustained, widespread, and persistent vascular dysfunction is present in Long COVID and that this dysfunction rooted in thrombotic endothelialitis is central to [the broad spectrum relapsing and remitting or persistent] symptoms.
In Long COVID, persistent endothelial cell dysfunction, clotting abnormalities (persistent microclot formation), and platelet hyperactivation have been noted as significant and ongoing pathological processes, thought to be accompanied by viral (or spike protein) persistence, immunological factors, and latent virus reactivation.
The authors state that overall, they "emphasize the critical role of cellular health in managing Long COVID and highlight the need for early intervention to prevent long-term vascular and cellular dysfunction".
In terms of therapeutics, they note that several have shown promise in the treatment of Long COVID. Anticoagulants such as non vitamin K antagonist oral anticoagulants and antiplatelet agents, for example aspirin and clopidogrel, have demonstrated potential in individuals with Long COVID, although the drug combinations need be investigated in a trial.

Study authors note that "These findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases.

This study developed research indices for characterizing pediatric PASC. Symptom patterns were similar but distinguishable between school-age children and adolescents, highlighting the importance of characterizing PASC separately in different age groups.
Kleinman is also noted separately as stating that "We have convincing evidence that COVID-19 is not just a mild, benign illness for children. There are children who are clearly disabled by Long Covid for long periods of time"

The author's study stating the incidence of Post Covid Condition in children was 'strikingly low' has been withdrawn due to methodological (analytical) errors in the original report that impacted the author's estimate of prevalence in children and adolescents and their reported associations between pre- and post–COVID-19 symptoms.
Corrections included:
We had concluded that the incidence of PCC was 0.4% (1/271). In correcting these errors, we found that the incidence of PCC was 1.4% (4/286)

Elevated incidence of type 2 diabetes after COVID-19 is greater, and persists for longer, in people who were hospitalised with COVID-19 than in those who were not, and is markedly less apparent in people who have been vaccinated against COVID-19. Testing for type 2 diabetes after severe COVID-19 and the promotion of vaccination are important tools in addressing this public health problem.

Children hospitalized with MIS-C or COVID-19 at 3 US hospitals from March 2020, through February 2021 were followed to assess health through 2 years post-hospitalization using medical records and patient surveys.
The study concludes that "Approximately 20% of children with MIS-C and COVID-19 continued to have symptoms including fatigue and headache >1 year after hospital discharge. The duration of these findings emphasizes the importance of providers following patients until sequelae have resolved."

In this study, seventy-one percent met criteria for an orthostatic condition, including postural orthostatic tachycardia syndrome (POTS), orthostatic tachycardia (OT), classic orthostatic hypotension (OH), delayed OH, and orthostatic hypertension.
The authors state "Our findings suggest that OI is common in pediatric long COVID, necessitating appropriate clinical screening and treatment".

SARS-CoV-2 infection during pregnancy can be transmitted vertically through the placenta, both in utero and perinatally, affecting the maternal–fetal immune interface and placental function. Viral infections during pregnancy have been linked to central nervous system development impairments and disorders such as autism. Changes in the structure and function of the respiratory, immune, and visceral systems have also been reported. SARS-CoV-2 infection during pregnancy has been linked with increased risks of stillbirth and preterm birth.
However, the mechanisms involved remain unclear and may include cytokine storms, macrophage mediation, genetic mutations, methylation, and other epigenetic changes.
Exploring the protective effects of antiviral treatment and other interventions in animal and clinical studies may help improve outcomes.
Future long-term studies may help provide evidence that can inform interventions to reduce the risk of adverse outcomes.

KEY POINTS
Post-acute sequelae of SARS CoV-2 infection (PASC) in adolescents and young adults
(AYAs) presents heterogeneously, often with multisystem involvement.
Between 3 and 6 months after infection, the most common persistent symptoms reported
are fever, sore throat, fatigue or muscle weakness, and sleep disturbances.
A subset of AYAs with persistent symptoms 6 months post-acute SARS CoV-2 infection
meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome, among whom fatigue, cognitive difficulties, post-exertional malaise, sleep disturbance, and symptoms
of orthostatic intolerance are most common.
PASC can be incredibly debilitating for AYAs in physical, social, and emotional domains
which may interrupt normal adolescent development and transition to adulthood.
Primary care providers have a key role in initial diagnosis, assessment, and treatment for
the numerous AYAs affected by PASC

In this article, authors present a case of a female rheumatoid arthritis patient who developed autoimmune thyroid disease, latent autoimmune diabetes of adults (LADA), and pernicious anemia after SARS-CoV-2 infection.
They state that "A notable aspect of Long COVID-19 is the emergence of new-onset autoimmune diseases that could be triggered in predisposed patients with altered immune responses. Common autoimmune conditions that arise in post-COVID patients include autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, etc."

SARS-CoV-2 infection leads to acute and post-acute sequelae in nearly every organ system. A substantial—and largely consistent—body of evidence has emerged over the past 4 years of the COVID-19 pandemic that describes the development of hyperglycaemia after SARS-CoV-2 infection in both the acute and post-acute phase of the infection.
Taylor's study adds further insight, showing that the risk of incident diabetes (type 2, type 1, and gestational diabetes) was higher after COVID-19 than before or in the absence of COVID-19 in each of the pre-vaccination, vaccinated, and unvaccinated cohorts. The authors report that the risk of type 2 diabetes remained high beyond the first year after SARS-CoV-2 infection.
135 per 100 000 people diagnosed with COVID-19 in the pre-vaccination cohort, 58 in the vaccinated cohort, and 225 in the unvaccinated cohort. The added burden due to SARS-CoV-2 infection represents a 15% increase in new cases,