Covid19-Sources

Among 5 899 170 individuals, COVID-19 admissions (n=24 400) were more frequent than influenza admissions (n=8385; aIRR 2·04 [95% CI 1·38–3·02]), particularly during the first year (May, 2022, to May, 2023) versus the second year (May, 2023, to June, 2024; p=0·0096), in the summer versus the winter (p0·0001), and among people aged 65 years or older versus younger than 65 years (p0·0001). The number of deaths was also higher for patients with COVID-19 (n=2361) than patients with influenza (n=489, aIRR 3·19 [95% CI 2·24–4·53]). Among patients admitted in the winter (n=19 286), the risk of mortality from COVID-19 was higher than for influenza (aRR 1·23 [95% CI 1·08–1·37]), particularly among those without COVID-19 and influenza vaccination (1·36 [1·05–1·67]), with comorbidities (1·27 [1·11–1·43]), and who were male (1·36 [1·14–1·59]).

Medical News: A team of researchers from the University of Iowa-USA has made significant discoveries about how certain lung cells survive acute SARS-CoV-2 infection and play a role in both inflammation and lung regeneration. Their findings provide a new understanding of the aftermath of severe COVID-19 cases, particularly how the body recovers and why some patients experience long-term symptoms. T...

DMZ – POLITIK / WISSEN / GESUNDHEIT ¦ AA ¦ Der Beitrag im "Pandemic Accountability Index" (Pandemie-Verantwortlichkeitsindex) vom letzten November, in dem über hundert Studien und Artikel zu den Auswirkungen des SARS-CoV-2-Virus auf den Körper berichtet wurde, ist mittlerweile über sechs Monate alt. Seitdem wurden weitere Forschungsergebnisse veröffentlicht. Es ist daher an der Zeit, unser Verständnis dafür zu aktualisieren, warum es so wichtig ist, Infektionen mit diesem gefährlichen und behindernden Virus zu verhindern. Laut der Weltgesundheitsorganisation (WHO) leiden allein in Europa über 36 Millionen Menschen an Langzeitfolgen von COVID, einem Oberbegriff für zahlreiche medizinische Komplikationen. Diejenigen, die behauptet haben, dass SARS-CoV-2 relativ harmlos oder "mild" sei und COVID-19 "nur eine Erkältung/Grippe" sei, müssen sich mit der ständig wachsenden Anzahl wissenschaftlicher Forschungsergebnisse auseinandersetzen, die seitdem veröffentlicht wurden. Kinder und COVID: COVID-19 ist eine der häufigsten Todesursachen bei Kindern und Jugendlichen in den USA (University of Oxford). Anstieg von Diabetes bei Kindern und Jugendlichen (Jama Network). Auch milde Infektionen können zu langfristigen Folgen führen, einschließlich Long-COVID (University of Minnesota). Mehr als 70% der Haushaltsübertragungen von COVID in den USA gehen von Kindern aus (CIDRAP). Kinder können nach einer asymptomatischen oder milden COVID-19-Erkrankung langfristige Herzmuskeldeformationen entwickeln (MDPI Open Access Journals). Langzeitfolgen bei Jugendlichen und jungen Erwachsenen nach mildem COVID-19 (Frontiers in Immunology). Einige Kinder zeigen nach einer COVID-19-Infektion Symptome wie Fieber, Erbrechen und Augenschmerzen (NHK). COVID-19 kann bei Kindern autoimmune Reaktionen auslösen (HCPLive). Erhöhte Raten von Asthma, Myokarditis, Diabetes und anderen Erkrankungen bei Kindern mit bestätigtem COVID-19 (Medical Journal of Australia). Über 30% der Kinder zeigen auch nach 2 Monaten noch Symptome, und 2,3% haben nach 6 Monaten immer noch anhaltende Symptome (Frontiers in Pediatrics). Das Immunsystem von Kindern entwickelt keine "adaptiven" Erinnerungen, die vor einer erneuten SARS-CoV-2-Infektion schützen (Garvan Institute of Medical Research). Die Prävalenz von Langzeitfolgen bei COVID-19 liegt bei 23,36% (ScienceDirect). Die Omikron-Variante verursacht siebenmal mehr Todesfälle bei hospitalisierten Kindern als die Influenza (South China Morning Post). In Ohio haben zwischen 30.000 und 70.000 Kinder Long COVID (US News). COVID-19 kann zu Herzerkrankungen bei Kindern führen (MDPI Open Access Journals). Entzündliche Erkrankungen bei Kindern nach COVID-19 (ScienceDirect). Neurologische Komplikationen nach COVID-19 bei Kindern (American Academy of Pediatrics). Augenmanifestationen von COVID-19 bei Kindern (SageJournals). Beeinträchtigungen der Gesundheit bei Kindern und Jugendlichen nach einer COVID-19-Erkrankung (American Academy of Pediatrics). Nahezu alle mit COVID-19 infizierten Kinder zeigen Anzeichen von Schädigung der Blutgefäße (Blood Advances). Eine Studie zeigt, dass vorherige COVID-19-Infektionen mit einem signifikant erhöhten Risiko für RSV-Infektionen bei Kindern in Verbindung gebracht werden (medRxiv). Zwischen 12 und 16% der Kinder und Jugendlichen, die mit Omikron infiziert waren, erfüllen die Definition von Long COVID (Journal of Pediatrics). Diabetes-Typ-1-Inzidenz und -Risiko bei Kindern mit einer COVID-19-Diagnose (Jama Network). Prävalenz von Long COVID bei Kindern und Jugendlichen beträgt 25,24%, am häufigsten mit Stimmungssymptomen (Nature). Ungewöhnlicher Anstieg von Hirnabszessen bei amerikanischen Kindern (CDC). Veränderte Verformung der roten Blutkörperchen bei Kindern und Jugendlichen nach SARS-CoV-2-Infektion (Nature). Kinder haben ein ähnliches Risiko für Langzeitfolgen von Long COVID bei einer erneuten Infektion wie bei der Erstinfektion (Journal of Pediatrics). SARS-CoV-2 kann sich über Wochen bis Monate systemisch ausbreiten und persistieren, unabhängig von der Schwere der Erkrankung (Lancet). Originallinks: COVID-19 is a leading cause of death in children and young people in the US (University of Oxford) Surge in child and teen diabetes (Jama Network) “Two US studies describe pediatric COVID...7.0% of hospitalized children developed neurologic complications such as seizures...even mild infections can lead to long COVID.” (University of Minnesota) More than 70% of US household COVID spread started with a child (CIDRAP) "Persistence of LV myocardial deformation abnormalities in previously healthy children with an asymptomatic or mildly symptomatic COVID-19 course after an average follow-up of 148 ± 68 days.” (MDPI Open Access Journals) “Inflammatory markers and pulmonary function in adolescents and young adults 6 months after mild COVID-19” (Frontiers in Immunology) “Fever, vomiting, and eye pain are a few of the symptoms afflicting a small number of children after they have been infected with COVID-19.” (NHK) COVID-19 May Trigger Autoimmune Responses in Children (HCPLive) “…increased rates of asthma, myocarditis and cardiomyopathy, cardiac dysrhythmias, diabetes, renal failure, venous thromboembolism, and coagulation disorders in children with laboratory‐confirmed COVID‐19 compared with children without COVID‐19.” (Medical Journal of Australia) “32.6% of the children had persistent symptoms at 2 months, 9.3% at 4 months, and 2.3% at 6 months” (Frontiers in Pediatrics) Children’s immune systems do not develop ‘adaptive’ memory to protect against second time SARS-CoV-2 infection (Garvan Institute of Medical Research) Based on 40 studies with 12,424 individuals, the pooled prevalence of any long COVID was 23.36 % (ScienceDirect) “Omicron strain causes 7 times more deaths among hospitalised children than influenza” (South China Morning Post) “In Ohio, between 30,000 and 70,000 children have long COVID.” (US News) COVID-19 Heart Lesions in Children: Clinical, Diagnostic and Immunological Changes (MDPI Open Access Journals) Multisystem inflammatory syndrome in children: A dysregulated autoimmune disorder following COVID-19 (ScienceDirect) COVID-19 and Acute Neurologic Complications in Children (American Academy of Pediatrics) Ocular manifestations of COVID-19 in pediatric patients (SageJournals) Health Impairments in Children and Adolescents After Hospitalization for Acute COVID-19 or MIS-C (American Academy of Pediatrics) "Virtually all children infected with COVID-19 show signs of blood vessel damage" (Blood Advances) "Findings from our study support that prior COVID-19 infection was associated with a significantly increased risk for RSV infection and was a driving force for the 2022 surge of severe pediatric RSV cases in the US." (medRxiv) “12-16% children and youth infected with Omicron met the research definition of #LongCovid at 3 and 6 months after infection, with no evidence of difference between cases of first-positive and reinfection” (Journal of Pediatrics) Type 1 Diabetes Incidence and Risk in Children With a Diagnosis of COVID-19 (Jama Network) Long-COVID in children and adolescents: prevalence of long-COVID was 25.24%, most prevalent clinical: mood symptoms (16.50%) - (Nature) Abnormal Surge of Brain Abscesses in American Children, CDC Says (ScienceAlert) Increased red blood cell deformation in children and adolescents after SARS-CoV-2 infection (Nature) Children are at as much risk of Long COVID disability from reinfection as they are from primary infection (Journal of Pediatrics) “in children, independent from disease severity, SARS-CoV-2 can spread systemically and persist for weeks to months.” (Lancet) NEUROLOGISCHE BEEINTRÄCHTIGUNGEN: Geruchs- und Geschmacksstörungen nach COVID-19 (BMJ). Neuropsychologische Defizite bei Patienten mit anhaltenden COVID-19-Symptomen (Nature). Neuroinflammation nach COVID-19 mit anhaltenden depressiven und kognitiven Symptomen (JAMA Psychiatry). SARS-CoV-2 fördert die Beseitigung synaptischer Verbindungen durch Mikrogliazellen im menschlichen Gehirn (Nature). Langfristige Auswirkungen von COVID-19 auf kognitive Funktionen bis zu 6 Monate nach der Entlassung: Rolle von Depressionen und Auswirkungen auf die Lebensqualität (Springer Link). SARS-CoV-2 ist mit Veränderungen der Gehirnstruktur verbunden (Nature). Jeder vierte Patient zeigt kognitive Defizite nach einem milden COVID-19-Verlauf (NIH). Neurokognitive und psychiatrische Symptome nach COVID-19-Infektion: Nachweise aus Labor- und Bevölkerungsstudien (ScienceDirect). COVID-19 und kognitive Beeinträchtigungen: Neuroinvasive und Blut-Hirn-Schrankenstörungen (Journal of Neuroinflammation). COVID-19 kann dazu führen, dass Gehirnzellen abnormal fusionieren und Beeinträchtigungen der Gehirnfunktion verursachen, bei 10% der untersuchten Fälle kommt die neuronale Aktivität vollständig zum Stillstand (ScienceAdvances). COVID-19 kann auch durch Hyperaktivierung der Immunantwort, Zelltod oder Entzündungen verschiedene Hirnregionen beeinträchtigen und zu Gedächtnisstörungen führen (CIDRAP). Rasche Verschlechterung der Demenz nach COVID-19 (NIH). Originallinks: Smell and taste dysfunction after covid-19 (BMJ) Neuropsychological deficits in patients with persistent COVID-19 symptoms (Nature) Neuroinflammation After COVID-19 With Persistent Depressive and Cognitive Symptoms (JAMA Psychiatry) SARS-CoV-2 promotes microglial synapse elimination in human brain organoids (Nature) Long-term consequences of COVID-19 on cognitive functioning up to 6 months after discharge: role of depression and impact on quality of life (Springer Link) SARS-CoV-2 is associated with changes in brain structure (Nature) 1 in 4 Showing Cognitive Deficits After Mild Case (NIH) Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies (ScienceDirect) COVID-19 and cognitive impairment: neuroinvasive and blood‒brain barrier dysfunction (Journal of Neuroinflammation) Covid cause...

Ibargüen-González, Heller et al. analyze plasma levels of pancreatic enzymes and inflammatory markers in a retrospective cohort study of 120 COVID-19 patients. Host factor PLAC8 is found to be required for SARS-CoV-2 pancreatic infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown diverse life-threatening effects, most of which are considered short-term. In addition to its short-term effects, which has claimed many millions of lives since 2019, the long-term complications of this virus are still under investigation. Similar to many oncogenic viruses, it has been hypothesized that SARS-CoV-2 employs various strategies to cause cancer in different organs. These include leveraging the renin angiotensin system, altering tumor suppressing pathways by means of its nonstructural proteins, and triggering inflammatory cascades by enhancing cytokine production in the form of a “cytokine storm” paving the way for the emergence of cancer stem cells in target organs. Since infection with SARS-CoV-2 occurs in several organs either directly or indirectly, it is expected that cancer stem cells may develop in multiple organs. Thus, we have reviewed the impact of coronavirus disease 2019 (COVID-19) on the vulnerability and susceptibility of specific organs to cancer development. It is important to note that the cancer-related effects of SARS-CoV-2 proposed in this article are based on the ability of the virus and its proteins to cause cancer but that the long-term consequences of this infection will only be illustrated in the long run.

Blood biomarkers in a middle-aged population suggest that SARS-CoV-2 infection is associated with greater brain β-amyloid plaque accumulation.

COVID-19, even in mild cases, is linked to changes in Alzheimer’s disease-related brain biomarkers comparable to four years of aging. This study raises concerns about long-term neurological risks and cognitive decline post-COVID.

Two distinct patterns in the protective effect of natural infection against reinfection in the Omicron variant versus pre-Omicron eras show that SARS-CoV-2 immune protection is shaped by dynamic interaction between host immunity and viral evolution.

Medical News: In the ongoing exploration of COVID-19’s far-reaching impacts on human health, researchers have uncovered a significant connection between the virus and reversible cerebral vasoconstriction syndrome (RCVS), a condition marked by temporary constriction of blood vessels in the brain. While RCVS is not a new medical phenomenon, its association with COVID-19 infection has only rece...

Medical News: Understanding the Threat of Nontuberculous Mycobacteria Nontuberculous mycobacteria (NTM) infections have been increasingly recognized as a major health concern, particularly in developed countries such as the United States. Unlike Mycobacterium tuberculosis, which causes tuberculosis (TB), NTM is commonly found in natural environments like soil, water, and food. While most people a...

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, we 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. In this review, we 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. We 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 COVID-19 pandemic has caused numerous deaths worldwide. Despite the mitigation of infection manifestations in recent months, the possible conseque…

Background COVID-19 is a disease that affects multiple organs and is believed to have an impact on the function of the heart muscle. Initial findings from hospitalized COVID-19 patients indicate the presence of myocardial injury characterized by increased levels of high-sensitive troponin. The causes of myocardial damage are diverse and not completely comprehended. Methods A three-dimensional echocardiogram (3DE) accurately measures the volume of the left ventricle (LV) and its function, both globally and regionally. It eliminates the subjective nature of two-dimensional echocardiography (2DE) when evaluating irregularities in the movement of the LV walls. This study sought to assess the left ventricular systolic function in 150 individuals who had recovered from COVID-19 and were experiencing post-COVID symptoms such as dyspnea, palpitation, or chest discomfort using 3DE. Results Our investigation revealed a notable statistical correlation (p-value of  0.001) between patients who had post-COVID-19 syndrome and reported enduring symptoms such as shortness of breath, or chest discomfort, and various 3D echocardiographic strain patterns (the mean GLS% in the cases group was − 16.06 ± 4.36, whereas in the control group it was − 17.9 ± 2.57). Subclinical myocardial dysfunction, as shown by a decrease in left ventricular global longitudinal strain (LV-GLS), is common in over 85% of patients with post-COVID-19 syndrome. However, more commonly observed indicators of left ventricular (LV) function, such as lower ejection fraction (EF) and anomalies in wall motion, were less frequently found. Conclusion Our study findings suggest that persons who developed symptoms such as difficulty breathing, rapid heartbeat, or chest pain following their recovery from COVID-19 exhibited a reduction in left ventricular global longitudinal strain (LV-GLS) as measured by three-dimensional echocardiography (3DE). Ongoing research is focused on determining the mechanism of heart damage in COVID-19 infection.

Now 6 Ongoing Clinical Trials in the United States

Nirmatrelvir-ritonavir is an effective treatment for SARS-CoV-2. In a subset of individuals treated with nirmatrelvir-ritonavir, the initial reduction in viral load is followed by viral rebound once treatment is stopped. We show that the timing of ...

Dass Corona mehr als eine Atemwegserkrankung ist, ist lange bekannt. Nun wird deutlich: Eine Infektion kann auch schwere Folgen für das Gehirn haben.

The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause of post-acute sequelae after SARS-CoV-2 infection or COVID-19 vaccination. COVID-19 vaccines utilize a modified, stabilized prefusion spike ...

Treating COVID, long-haul, and vaccine side-effects ASAP is key for best outcomes.

The SARS-CoV-2 global pandemic has highlighted the risk of nosocomial infections of airborne viruses to patient populations around the world. Increased use of mechanical ventilation and portable air cleaners (PACs) have been suggested as methods to mitigate this risk, but the introduction of new air flows to indoor areas can have complex and potentially unforeseen consequences. We used particle counters to investigate the effect of using built-in mechanical ventilation and/or PACs in a typical hospital outpatients’ clinic upon the spread of aerosols produced by an aerosol generator. A variety of scenarios was investigated, examining particle movement to a neighboring room, throughout the whole clinic, and from one room to another at the far side of the clinic. Whilst both built-in ventilation and PACs may reduce particle migration in some scenarios by up to 96%, use of the same PACs may lead to unexpectedly increased aerosol migration of 29% between neighboring rooms, and use of built-in supply ventilation may increase aerosol migration across the clinic by up to 5.5 times. These increases are most likely due to the introduction of air flows from the outlets of these devices, providing aerosols with enough momentum to traverse the distance between relatively remote locations or creating recirculation regions that pull aerosols out of one room and push them into another. Accordingly, in order to effectively deploy these useful mitigations to their full potential and not simply displace the risk of nosocomial infection, careful consideration of placement and resultant air flow dynamics is required.

In response to the ongoing evolution of SARS-CoV-2, vaccine manufacturers have released updated COVID-19 vaccines annually since 2022. For much of 2024, the global spread was dominated by the JN.1 lineage of viruses,1 which are antigenically quite distant from the XBB.1.5 variant that was used in the previous vaccine booster.2 In August 2024, the US Food and Drug Administration authorised two updated mRNA vaccines (Pfizer–BioNTech and Moderna) based on the spike sequence of KP.2, a subvariant in the JN.1 lineage.3 In the UK and the EU, a KP.2-based mRNA vaccine (BioNTech) was also authorised later in the year.4,5 We have now provided the first indication of the acute boosting effect of updated KP.2 monovalent mRNA vaccines (KP.2 MV) on serum SARS-CoV-2 neutralising antibodies in humans.Since the authorisation of the updated vaccine boosters, SARS-CoV-2 has evolved beyond KP.2, with the subvariant KP.3.1.1 becoming dominant globally and the subvariant XEC now gaining traction rapidly.1 KP.2 contains Arg346Thr, Phe456Leu, and Val1104Leu mutations in spike, in addition to those present in the parental JN.1 (figure A). Both KP.3.1.1 and XEC share Phe456Leu and Val1104Leu mutations found in KP.2, along with Gln493Glu, which is absent in KP.2. In addition, KP.3.1.1 harbors the Ser31del mutation, whereas XEC carries Thr22Asn and Phe59Ser mutations; neither KP.3.1.1 nor XEC possess the Arg346Thr mutation (figure A). The effectiveness of the updated KP.2 MV boosters on neutralising antibodies in human serum against recently dominant subvariants has yet to be reported.

A new study found severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was associated with the rapid growth of plaque in the coronary arteries and an increased risk of cardiovascular events.

A Beginner's Guide

There are no approved treatments for post-COVID-19 condition (also known as long COVID), a debilitating disease state following SARS-CoV-2 infection that is estimated to affect tens of millions of people. 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, we outline these and other key considerations, with the goal of informing the design, implementation, and interpretation of trials in this rapidly growing field. Our 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.

Background Since 2022, Norway has employed a vaccine-only COVID-19 strategy. Primary healthcare in Norway uses International Classification of Primary Care version 2 (ICPC-2) codes. This study aims to systematically compare medically certified sick leave and primary healthcare consultations in 2023 with the pre-pandemic 2010–2019 trends, and subsequently estimate the magnitude of these changes. Methods For the respective outcomes of (A) working person-years lost to medically certified sick leave (WYLSL) and (B) number of primary healthcare consultations, 556 and 85 ICPC-2 code combinations were extracted from the Norwegian Labour and Welfare Administration’s sick leave registry and the Norwegian Syndromic Surveillance System. For each ICPC-2 code combination, a Bayesian linear regression was performed using data between 2010 and 2019 to estimate an expected baseline for 2023, which was then used to calculate the deviation from the pre-pandemic trend. A false discovery rate of 5% was used to account for multiple testing. Results All years from 2020 to 2023 had excess WYLSL, corresponding to 14,491 (90% PI: 8,935 to 20,016) in 2020, 12,911 (90% PI: 5,916 to 19,996) in 2021, 21,263 (90% PI: 12,627 to 29,864) in 2022, and 24,466 (90% PI: 14,023 to 34,705) in 2023. This corresponded to an economic loss of approximately 1.5 billion USD in 2023. Excess WYLSL due to A* (General and unspecified) increased from 2020 to 2023, with an estimated excess of 4,136 WYLSL in 2023 (69% higher than expected). More than half of this increase was explained by A04 (Weakness/tiredness general), whose excess WYLSL in 2023 were estimated at 2,640 (80% higher than expected). The excess in A04 (Weakness/tiredness general) corresponded to an economic loss of 161 million USD and accounted for 11% of the total excess WYLSL in 2023. The excess WYLSL in R* (Respiratory) in 2023 was 3,408, which correspond to an economic loss of 207 million USD and accounted for 14% of the total excess in 2023. Conclusions Significant excesses in working person-years lost to medically certified sick leave and primary healthcare consultations in 2023. A sizable proportion of the excesses were due to diseases/symptoms associated with acute and post-acute sequelae of COVID-19.

Introduction Effective immune protection against SARS-CoV-2 infection and severe COVID-19 disease continues to change due to viral evolution and waning immunity. We estimated population-level immunity to SARS-CoV-2 for each of the fifty United States (U.S.) and the District of Columbia from January 2020 through December 2023. Methods We updated a model of SARS-CoV-2 infections to align with the latest evidence on SARS-CoV-2 natural history and waning of immunity, and to integrate various data sources available throughout the pandemic. We used this model to produce population estimates of effective protection against SARS-CoV-2 infection and severe COVID-19 disease. Results On December 30, 2023, 99.9% of the U.S. population had experienced immunological exposure to SARS-CoV-2 through infection and/or vaccination, with 99.4% (95% credible interval (CrI): 92.4-100%) having had at least one SARS-CoV-2 infection. Despite this high exposure, the average population-level protection against infection was 53.6% (95% CrI: 38.7-71.5%). Population-level protection against severe disease was 82.6% (95% CrI: 71.5-91.7%). Discussion A new wave of SARS-CoV-2 infections and COVID-19-associated hospitalizations began near the end of 2023, with the introduction of the JN.1 variant. This upturn suggests that the U.S. population remains at risk of SARS-CoV-2 infection and severe COVID-19 disease despite the high level of cumulative exposure in the United States. This decline in effective protection is likely due to both waning and continued viral evolution. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This project has been funded (in part) by contract number 200-2016-91779 with the Centers for Disease Control and Prevention (CDC) and funding from the Centers for Disease Control and Prevention through the Council of State and Territorial Epidemiologists (Grant Number NU3OT000297). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All code and data used in this analysis are available on GitHub (). The produced datasets are available on the Harvard Dataverse ().