Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants (preprint)

The spike glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to accumulate substitutions, leading to breakthrough infections of vaccinated individuals and prompting the development of updated booster vaccines. Here, we determined the specificity and functionality of antibody and B cell responses following exposure to BA.5 and XBB variants in individuals who received ancestral SARS-CoV-2 mRNA vaccines. BA.5 exposures elicited antibody responses that primarily targeted epitopes conserved between the BA.5 and ancestral spike, with poor reactivity to the XBB.1.5 variant. XBB exposures also elicited antibody responses that targeted epitopes conserved between the XBB.1.5 and ancestral spike. However, unlike BA.5, a single XBB exposure elicited low levels of XBB.1.5-specific antibodies and B cells in some individuals. Pre-existing cross-reactive B cells and antibodies were correlated with stronger overall responses to XBB but weaker XBB-specific responses, suggesting that baseline immunity influences the activation of variant-specific SARS-CoV-2 responses. HighlightsO_LIVariant breakthrough infections boost ancestral cross-reactive antibodies and B cells C_LIO_LIFirst and second BA.5 exposures fail to elicit variant-specific antibodies and B cells C_LIO_LIXBB infections and monovalent vaccinations elicit XBB.1.5-specific responses in some individuals C_LIO_LIXBB.1.5-specific responses correlate with low levels of pre-existing humoral immunity C_LI

Personal risk or societal benefit? Investigating adults' support for COVID-19 childhood vaccination.

Parental hesitancy poses a serious threat to the success of the COVID-19 childhood vaccination campaign. We investigate whether adults' opinions on childhood vaccination can be influenced via two survey experiments in Italy (n = 3,633 participants) and the UK (n = 3,314 participants). Respondents were randomly assigned to: a "risk treatment" that highlighted the potential risks of COVID-19 to a child, a "herd immunity treatment" that emphasized the community benefits of pediatric vaccination, or a control message. Participants' probability of supporting COVID-19 childhood vaccination was then assessed on a 0-100 scale. We find that the "risk treatment" reduced the proportion of Italian parents strongly against vaccination by up to 29.6 %, while increasing the proportion of neutral parents by up to 45.0 %. The "herd immunity treatment", instead, was only effective among non-parents, resulting in a lower proportion of individuals against pediatric vaccination and a higher proportion of individuals in favor (both shifted by around 20 %).

Aerosol charge neutralization and its impact on particle filtration efficiency of common face mask materials

Despite the significant increase in research on mask filtration testing since the COVID-19 pandemic, there remains considerable ambiguity regarding which parameters affect particle filtration efficiency (PFE) and how differences in standard testing protocols can lead to divergent PFE values. We evaluated the PFE (and differential pressure) of several common face masks and community face mask materials including woven cotton, spunbond polypropylene, and meltblown polypropylene, testing in accordance with ASTM F2100/2299 standards for medical masks, using polystyrene latex (PSL) aerosol, as well as NIOSH standards for respirators, using NaCl aerosol. In both cases, PFE was measured with and without aerosol charge neutralization, which is used to bring the particle population to a known, equilibrium bipolar charge distribution. Aerosols of either composition that were not neutralized (untreated) led to significant increases in measured PFE, especially in the case of PSL. In contrast, effective neutralization led to lower PFE measurements that also showed little to no dependence on aerosol composition across most materials. To investigate further, the bipolar charge distributions of PSL and NaCl aerosols, both neutralized and untreated, were characterized using an aerodynamic aerosol classifier operated in tandem with a scanning mobility particle sizer (AAC-SMPS). This technique illustrated the differences in the distribution of particle charge states between PSL and NaCl aerosols of the same size, and between PSL particles of different sizes, revealing the presence of highly charged particles in many cases. Most importantly, the equilibrium charge distribution after neutralization is shown to be independent of particle composition or initial charge distribution, highlighting the crucial role of aerosol charge neutralizers in preventing overestimates of mask performance (due to electrostatic effects) and promoting consistency in standard testing procedures.

Impact of the COVID-19 pandemic on the management of risk factors in patients with stable atherosclerotic vascular disease.

Background: Effective control of risk factors in patients with ASCVD is important to reduce recurrent cardiovascular events. However, many ASCVD patients do not have their risk factors controlled, and this may have worsened during the COVID-19 pandemic. Methods: We retrospectively evaluated risk factor control among 24,760 ASCVD patients who had at least 1 outpatient encounter both pre-pandemic and during the first year of the pandemic. Risk factors were uncontrolled if the blood pressure (BP) ≥ 130/80 mm Hg, LDL-C ≥ 70 mg/dL, HgbA1c ≥ 7 for diabetic patients, and patients were current smokers. Results: During the pandemic, many patients had their risk factors unmonitored. BP control worsened (BP ≥ 130/80 mmHg, 64.2 vs 65.7%; p = 0.01), while lipid management improved with more patients on a high-intensity statin (38.9 vs 43.9%; p<0.001) and more achieving an LDL-C < 70 mg/dL, less patients were smoking (7.4 vs 6.7%; p<0.001), and diabetic control was unchanged pre vs during the pandemic. Black (OR 1.53 [1.02-2.31]) and younger aged patients (OR 1.008 [1.001-1.015]) were significantly more likely to have missing or uncontrolled risk factors during the pandemic. Conclusions: During the pandemic risk factors were more likely to be unmonitored. While measured blood pressure control worsened, lipid control and smoking improved. Although some cardiovascular risk factor control improved during the COVID-19 pandemic, overall control of cardiovascular risk factors in patients with ASCVD was suboptimal, especially in Black and younger patients. This puts many ASCVD patients at increased risk of a recurrent cardiovascular event.

Health Risks and Voting: Emphasizing Safety Measures Taken to Prevent COVID-19 Does Not Increase Willingness to Vote in Person

The COVID-19 pandemic made salient the risks posed by an infectious disease at a polling place. To what degree did such health risks, as with other changes to voting costs, affect the willingness to vote in person? Could highlighting safety measures reduce the association between COVID fears and unwillingness to vote in person? Using both a representative survey of Connecticut voters and a survey experiment, we examine whether concerns about health diminish willingness to vote in person. We find correlational evidence that those who are more worried about COVID-19 are less likely to report they will vote in person, even when considering risk mitigation efforts. We then present causal evidence that mentioning the safety measures being taken does little to offset the negative effect of priming COVID-19 risk on willingness to vote in person. These results contribute to a growing literature that assesses how health risks affect in person voting. [ FROM AUTHOR] Copyright of American Politics Research is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Predictors of Nonseroconversion after SARS-CoV-2 Infection.

Not all persons recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop SARS-CoV-2-specific antibodies. We show that nonseroconversion is associated with younger age and higher reverse transcription PCR cycle threshold values and identify SARS-CoV-2 viral loads in the nasopharynx as a major correlate of the systemic antibody response.

Cadaveric emergency cricothyrotomy training for non-surgeons using a bronchoscopy-enhanced curriculum.

BACKGROUND: Emergency cricothyrotomy training for non-surgeons is important as rare "cannot intubate or oxygenate events" may occur multiple times in a provider's career when surgical expertise is not immediately available. However, such training is highly variable and often infrequent, therefore, enhancing these experiences is important. RESEARCH QUESTION: Is bronchoscopy-enhanced cricothyrotomy training in cadavers feasible, and what are the potential benefits provided by this innovation for trainees? METHODS: This study was performed during implementation of a new program to train non-surgeon providers on cadaveric donors on our campus. Standard training with an instructional video and live coaching was enhanced by bronchoscopic visualization of the trachea allowing participants to review their technique after performing scalpel and Seldinger-technique procedures, and to review their colleagues' technique on live video. Feasibility was measured through assessing helpfulness for trainees, cost, setup time, quality of images, and operator needs. Footage from the bronchoscopy recordings was analyzed to assess puncture-to-tube time, safety errors, and evidence for a training effect within groups. Participants submitted pre- and post-session surveys assessing their levels of experience and gauging their confidence and anxiety with cricothyrotomies. RESULTS: The training program met feasibility criteria for low costs (<200 USD/donor), setup time (<30 minutes/donor), and operator needs (1/donor). Furthermore, all participants rated the cadaveric session as helpful. Participants demonstrated efficient technique, with a median puncture-to-tube time of 48.5 seconds. Bronchoscopy recordings from 24 analyzed videos revealed eight instances of sharp instruments puncturing the posterior tracheal wall (33% rate), and two instances of improper tube placement (8% rate). Sharp instruments reached potentially dangerous insertion depths beyond the midpoint of the anterior-posterior diameter of the trachea in 58.3% of videos. Bronchoscopic enhancement was rated as quite or extremely helpful for visualizing the trachea (83.3%) and to assess depth of instrumentation (91.7%). There was a significant average increase in confidence (64.4%, P<0.001) and average decrease in performance anxiety (-11.6%, P = 0.0328) after the session. A training effect was seem wherein the last trainee in each group had no posterior tracheal wall injuries. INTERPRETATION: Supplementing cadaveric emergent cricothyrotomy training programs with tracheal bronchoscopy is feasible, helpful to trainees, and meets prior documented times for efficient technique. Furthermore, it was successful in detecting technical errors that would have been missed in a standard training program. Bronchoscopic enhancement is a valuable addition to cricothyrotomy cadaveric training programs and may help avoid real-life complications.

T-Toxin Virulence Genes: Unconnected Dots in a Sea of Repeats.

In 1970, the Southern Corn Leaf Blight epidemic ravaged U.S. fields to great economic loss. The outbreak was caused by never-before-seen, supervirulent, Race T of the fungus Cochliobolus heterostrophus. The functional difference between Race T and O, the previously known, far less aggressive strain, is production of T-toxin, a host-selective polyketide. Supervirulence is associated with ~1 Mb of Race T-specific DNA; only a fraction encodes T-toxin biosynthetic genes (Tox1). Tox1 is genetically and physically complex, with unlinked loci (Tox1A, Tox1B) genetically inseparable from breakpoints of a Race O reciprocal translocation that generated hybrid Race T chromosomes. Previously, we identified 10 genes for T-toxin biosynthesis. Unfortunately, high-depth, short-read sequencing placed these genes on four small, unconnected scaffolds surrounded by repeated A+T rich sequence, concealing context. To sort out Tox1 topology and pinpoint the hypothetical Race O translocation breakpoints corresponding to Race T-specific insertions, we undertook PacBio long-read sequencing which revealed Tox1 gene arrangement and the breakpoints. Six Tox1A genes are arranged as three small islands in a Race T-specific sea (~634 kb) of repeats. Four Tox1B genes are linked, on a large loop of Race T-specific DNA (~210 kb). The race O breakpoints are short sequences of race O-specific DNA; corresponding positions in race T are large insertions of race T-specific, A+T rich DNA, often with similarity to transposable (predominantly Gypsy) elements. Nearby, are 'Voyager Starship' elements and DUF proteins. These elements may have facilitated Tox1 integration into progenitor Race O and promoted large scale recombination resulting in race T. IMPORTANCE In 1970 a corn disease epidemic ravaged fields in the United States to great economic loss. The outbreak was caused by a never-before seen, supervirulent strain of the fungal pathogen Cochliobolus heterostrophus. This was a plant disease epidemic, however, the current COVID-19 pandemic of humans is a stark reminder that novel, highly virulent, pathogens evolve with devastating consequences, no matter what the host-animal, plant, or other organism. Long read DNA sequencing technology allowed in depth structural comparisons between the sole, previously known, much less aggressive, version of the pathogen and the supervirulent version and revealed, in meticulous detail, the structure of the unique virulence-causing DNA. These data are foundational for future analysis of mechanisms of DNA acquisition from a foreign source.

Clinical Characteristics and Cause of Death Among Hospitalized Decedents With Cancer and COVID-19.

There is scant information on the clinical progression, end-of-life decisions, and cause of death of patients with cancer diagnosed with COVID-19. Therefore, we conducted a case series of patients admitted to a comprehensive cancer center who did not survive their hospitalization. To determine the cause of death, 3 board-certified intensivists reviewed the electronic medical records. Concordance regarding cause of death was calculated. Discrepancies were resolved through a joint case-by-case review and discussion among the 3 reviewers. During the study period, 551 patients with cancer and COVID-19 were admitted to a dedicated specialty unit; among them, 61 (11.6%) were nonsurvivors. Among nonsurvivors, 31 (51%) patients had hematologic cancers, and 29 (48%) had undergone cancer-directed chemotherapy within 3 months before admission. The median time to death was 15 days (95% confidence interval [CI], 11.8 to 18.2). There were no differences in time to death by cancer category or cancer treatment intent. The majority of decedents (84%) had full code status at admission; however, 53 (87%) had do-not-resuscitate orders at the time of death. Most deaths were deemed to be COVID-19 related (88.5%). The concordance between the reviewers for the cause of death was 78.7%. In contrast to the belief that COVID-19 decedents die because of their comorbidities, in our study only 1 of every 10 patients died of cancer-related causes. Full-scale interventions were offered to all patients irrespective of oncologic treatment intent. However, most decedents in this population preferred care with nonresuscitative measures rather than full support at the end of life.

Socioeconomic correlates of health outcomes and mental health disparity in a sample of cancer patients during the COVID-19 pandemic.

AIMS AND OBJECTIVES: To investigate socioeconomic, behavioural and healthcare delivery factors that are associated with health outcomes of cancer patients during the COVID-19 pandemic, especially among underserved cancer patients. BACKGROUND: Cancer patients are at a higher risk of adverse physical and mental health outcomes during the pandemic than those without cancer. DESIGN: Cross-sectional online survey. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines in this study. METHODS: The sample comprised 322 individuals diagnosed with incident cancer between January 2019 and January 2020. Demographically, 64% were female, 49% had a college degree, 12% were African American, and 88% were White (77% of the Whites were from metropolitan and 23% from nonmetropolitan areas). Descriptive analysis and multivariable regression analyses of global health status, depression and irritability were performed. RESULTS: After adjusting for demographic variables and comorbidity, the feelings of loneliness, crowded living space, lower confidence in taking preventive measures and less satisfaction with telehealth visits were significantly associated with poorer global health, depression and irritability. Daily exercise was associated with better global health, and difficulty in getting medicine was associated with depression and irritability. Moreover, African Americans who felt lonely reported more depression and irritability and those who had less confidence in taking preventive measures reported more irritability than Whites. Respondents having low income and feeling lonely reported more depression than others. CONCLUSIONS: In this study, socioeconomic factors (e.g. loneliness or crowded living conditions) were as important to health outcomes during the pandemic as behavioural (e.g. prevention and exercises) and quality-of-care factors (e.g. telehealth, access to medicine). Disparity was more pronounced in the mental health of African Americans and those with low incomes. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should promote social support and physical activity for improving health and reducing mental health disparities among cancer patients.

Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model (preprint)

Maternal antibodies (matAbs) protect against a myriad of pathogens early in life; however, these antibodies can also inhibit de novo immune responses against some vaccine platforms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) matAbs are efficiently transferred during pregnancy and protect infants against subsequent SARS-CoV-2 infections. It is unknown if matAbs inhibit immune responses elicited by different types of SARS-CoV-2 vaccines. Here, we established a mouse model to determine if SARS-CoV-2 spike-specific matAbs inhibit immune responses elicited by recombinant protein and nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccines. We found that SARS-CoV-2 mRNA-LNP vaccines elicited robust de novo antibody responses in mouse pups in the presence of matAbs. Recombinant protein vaccines were also able to circumvent the inhibitory effects of matAbs when adjuvants were co-administered. While additional studies need to be completed in humans, our studies raise the possibility that mRNA-LNP-based and adjuvanted protein-based SARS-CoV-2 vaccines have the potential to be effective when delivered very early in life.

Habitat Imaging Biomarkers for Diagnosis and Prognosis in Cancer Patients Infected with COVID-19.

OBJECTIVES: Cancer patients have worse outcomes from the COVID-19 infection and greater need for ventilator support and elevated mortality rates than the general population. However, previous artificial intelligence (AI) studies focused on patients without cancer to develop diagnosis and severity prediction models. Little is known about how the AI models perform in cancer patients. In this study, we aim to develop a computational framework for COVID-19 diagnosis and severity prediction particularly in a cancer population and further compare it head-to-head to a general population. METHODS: We have enrolled multi-center international cohorts with 531 CT scans from 502 general patients and 420 CT scans from 414 cancer patients. In particular, the habitat imaging pipeline was developed to quantify the complex infection patterns by partitioning the whole lung regions into phenotypically different subregions. Subsequently, various machine learning models nested with feature selection were built for COVID-19 detection and severity prediction. RESULTS: These models showed almost perfect performance in COVID-19 infection diagnosis and predicting its severity during cross validation. Our analysis revealed that models built separately on the cancer population performed significantly better than those built on the general population and locked to test on the cancer population. This may be because of the significant difference among the habitat features across the two different cohorts. CONCLUSIONS: Taken together, our habitat imaging analysis as a proof-of-concept study has highlighted the unique radiologic features of cancer patients and demonstrated effectiveness of CT-based machine learning model in informing COVID-19 management in the cancer population.

The Impact of the COVID-19 Pandemic on Tobacco Treatment Program Implementation at NCI-Designated Cancer Centers.

INTRODUCTION: The COVID-19 pandemic disrupted cancer screening and treatment delivery, but COVID-19's impact on tobacco cessation treatment for cancer patients who smoke has not been widely explored. METHODS: We conducted a sequential cross-sectional analysis of data collected from 34 NCI-designated cancer centers participating in NCI's Cancer Center Cessation Initiative (C3I), across three reporting periods: one prior to COVID-19 (January-June 2019) and two during the pandemic (January-June 2020, January-June 2021). Using McNemar's Test of Homogeneity, we assessed changes in services offered and implementation activities over time. RESULTS: The proportion of centers offering remote treatment services increased each year for Quitline referrals (56%, 68%, and 91%; p=.000), telephone counseling (59%, 79%, and 94%; p=.002), and referrals to Smokefree TXT (27%, 47%, and 56%; p=.006). Centers offering video-based counseling increased from 2020 to 2021 (18% to 59%; p=.006), Fewer than 10% of centers reported laying off tobacco treatment staff. Compared to early 2020, in 2021 C3I centers reported improvements in their ability to maintain staff and clinician morale, refer to external treatment services, train providers to deliver tobacco treatment, and modify clinical workflows. DISCUSSION: The COVID-19 pandemic necessitated rapid transition to new telehealth program delivery of tobacco treatment for patients with cancer. C3I cancer centers adjusted rapidly to challenges presented by the pandemic, with improvements reported in staff morale and ability to train providers, refer patients to tobacco treatment, and modify clinical workflows. These factors enabled C3I centers to sustain evidence-based tobacco treatment implementation during and beyond the COVID-19 pandemic. IMPLICATIONS: This work describes how NCI-designated cancer centers participating in the Cancer Center Cessation Initiative (C3I) adapted to challenges to sustain evidence-based tobacco use treatment programs during the COVID-19 pandemic. This work offers a model for resilience and rapid transition to remote tobacco treatment services delivery and proposes a policy and research agenda for telehealth services as an approach to sustaining evidence-based tobacco treatment programs.

Association between COVID-19 and Postoperative Neurological Complications and Antipsychotic Medication Use after Cancer Surgery: A Retrospective Study.

INTRODUCTION: Millions of Americans infected with the severe acute respiratory syndrome-associated coronavirus-19 (COVID-19) need oncologic surgery. Patients with acute or resolved COVID-19 illness complain of neuropsychiatric symptoms. How surgery affects postoperative neuropsychiatric outcomes such as delirium is unknown. We hypothesize that patients with a history of COVID-19 could have an exaggerated risk of developing postoperative delirium after undergoing major elective oncologic surgery. METHODS: We conducted a retrospective study to determine the association between COVID-19 status and antipsychotic drugs during postsurgical hospitalization as a surrogate of delirium. Secondary outcomes included 30 days of postoperative complications, length of stay, and mortality. Patients were grouped into pre-pandemic non-COVID-19 and COVID-19-positive groups. A 1:2 propensity score matching was used to minimize bias. A multivariable logistic regression model estimated the effects of important covariates on the use of postoperative psychotic medication. RESULTS: A total of 6003 patients were included in the study. Pre- and post-propensity score matching demonstrated that a history of preoperative COVID-19 did not increase the risk of antipsychotic medications postoperatively. However, respiratory and overall 30-day complications were higher in COVID-19 individuals than in pre-pandemic non-COVID-19 patients. The multivariate analysis showed that the odds of using postoperative antipsychotic medication use for the patients who had COVID-19 compared to those who did not have the infection were not significantly different. CONCLUSION: A preoperative diagnosis of COVID-19 did not increase the risk of postoperative antipsychotic medication use or neurological complications. More studies are needed to reproduce our results due to the increased concern of neurological events post-COVID-19 infection.

Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodies (preprint)

SARS-CoV-2 infection of vaccinated individuals is increasingly common but rarely results in severe disease, likely due to the enhanced potency and accelerated kinetics of memory immune responses. However, there have been few opportunities to rigorously study early recall responses during human viral infection. To better understand human immune memory and identify potential mediators of lasting vaccine efficacy, we used high-dimensional flow cytometry and SARS-CoV-2 antigen probes to examine immune responses in longitudinal samples from vaccinated individuals infected during the Omicron wave. These studies revealed heightened Spike-specific responses during infection of vaccinated compared to unvaccinated individuals. Spike-specific CD4 T cells and plasmablasts expanded and CD8 T cells were robustly activated during the first week. In contrast, memory B cell activation, neutralizing antibody production, and primary responses to non-Spike antigens occurred during the second week. Collectively, these data demonstrate the functionality of vaccine-primed immune memory and highlight memory T cells as rapid responders during SARS-CoV-2 infection.

Mucociliary transport deficiency and disease progression in Syrian hamsters with SARS-CoV-2 infection.

Substantial clinical evidence supports the notion that ciliary function in the airways is important in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, the extent or nature of impairment of mucociliary transport (MCT) in in vivo models remains unknown. We hypothesize that SARS-CoV-2 infection results in MCT deficiency in the airways of golden Syrian hamsters that precedes pathological injury in lung parenchyma. Micro-optical coherence tomography was used to quantitate functional changes in the MCT apparatus. Both genomic and subgenomic viral RNA pathological and physiological changes were monitored in parallel. We show that SARS-CoV-2 infection caused a 67% decrease in MCT rate as early as 2 days postinfection (dpi) in hamsters, principally due to 79% diminished airway coverage of motile cilia. Correlating quantitation of physiological, virological, and pathological changes reveals steadily descending infection from the upper airways to lower airways to lung parenchyma within 7 dpi. Our results indicate that functional deficits of the MCT apparatus are a key aspect of COVID-19 pathogenesis, may extend viral retention, and could pose a risk factor for secondary infection. Clinically, monitoring abnormal ciliated cell function may indicate disease progression. Therapies directed toward the MCT apparatus deserve further investigation.

Public Health Actions to Control Measles Among Afghan Evacuees During Operation Allies Welcome - United States, September-November 2021.

On August 29, 2021, the United States government oversaw the emergent establishment of Operation Allies Welcome (OAW), led by the U.S. Department of Homeland Security (DHS) and implemented by the U.S. Department of Defense (DoD) and U.S. Department of State (DoS), to safely resettle U.S. citizens and Afghan nationals from Afghanistan to the United States. Evacuees were temporarily housed at several overseas locations in Europe and Asia* before being transported via military and charter flights through two U.S. international airports, and onward to eight U.S. military bases,† with hotel A used for isolation and quarantine of persons with or exposed to certain infectious diseases.§ On August 30, CDC issued an Epi-X notice encouraging public health officials to maintain vigilance for measles among Afghan evacuees because of an ongoing measles outbreak in Afghanistan (25,988 clinical cases reported nationwide during January-November 2021) (1) and low routine measles vaccination coverage (66% and 43% for the first and second doses, respectively, in 2020) (2).

COVID-19 and children.

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in transmission, especially in schools and at home, is crucial to ensuring effective mitigation measures. Therefore, in addition to nonpharmaceutical interventions, such as improved ventilation, there is a strong case to vaccinate children so as to reduce possible long-term effects from infection and to decrease transmission. But questions remain about whether vaccination might skew immune responses to variants in the long term. As the experts discuss below, more is being learned about these important issues, but much more research is needed to understand the long-term effects of COVID-19 in children.