SARS-CoV-2 と COVID-19 に関する備忘録 Vol.40

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆Left ventricular assessment by 3D-echocardiography in post-COVID-19 syndrome【SPRINGER NATURE　2025年2月18日】

Abstract

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.

◆Reply to: Should we be careful with exercise in post-exertional malaise after Long COVID?【nature communications　2025年2月18日】

We thank Saris et al. for their interest in our recent paper, which focused on the skeletal muscle components of post-exertional malaise (PEM) in Long COVID patients. We did not address the efficacy of exercise as a treatment, but our findings do not support that deconditioning or bed rest explains the skeletal muscle abnormalities in Long COVID. PEM is a distinct symptom that is poorly understood and not analogous to other conditions. We caution against generalizing our results to all Long COVID patients or drawing causal conclusions beyond the study’s design, and we advocate adherence to established guidelines that recommend avoiding activities triggering PEM.

Whilst we recognize the exercise therapy experience of Saris et al. in patients with mitochondrial and neuromuscular diseases, we firmly reject the notion that our findings regarding post-exertional malaise (PEM) are not specific to Long COVID, nor that we address “how to treat this condition”. Saris et al. claim that “improvements in muscle fitness can act as therapy in Long COVID”, based on assumptions and experiences with other diseases. PEM is a specific symptom of many post-viral infection diseases (including Long COVID and ME/CFS) which is poorly understood, and poorly recognized by clinicians. As such, intense exercise above an unknown time- and patient-dependent PEM-inducing threshold is often avoided by patients, because it worsens their Long COVID symptoms. Therefore, it was the explicit goal of our study to examine the systemic and skeletal muscle component of PEM in Long COVID.

Importantly, our publication did not provide any statement about the merit or avoidance of exercise in treating patients with Long COVID, and we are therefore surprised that Saris and colleagues concluded this. We clearly understand that frequency, intensity and duration are important parameters of exercise training in improving aerobic fitness in healthy people. However, patients with Long COVID and PEM are unable to functionally recover completely after an exercise bout at a high intensity or duration, limiting their ability to frequently perform such exercise bouts. The interpretation of exercise-related results in Long COVID critically depends on which patients are included. Our patients could work ~5 h/week, and all experienced PEM, which is a key symptom in 87% of all Long COVID patients. Hence, our results should not be extrapolated to all Long COVID patients (i.e., those not suffering from PEM or with less debilitating symptoms, such as in a recent study). Further, our results cannot be extrapolated to applicability of exercise training for treatment, simply because we did not study this.

◆Reply to: Should we be careful with exercise in post-exertional malaise after Long COVID?【Nieuwsblad　2025年2月18日】

We melden ons vaker ziek op het werk: “De kost is aanzienlijk”

Een op de zeven werknemers in de privésector is langer dan een maand afwezig. Dat blijkt dinsdag uit cijfers over ziekteverzuim van het sociaal secretariaat SD Worx.

De HR-specialist baseert zich voor zijn analyse op gegevens van bijna 1 miljoen werknemers bij 38.000 Belgische bedrijven.

Het korte ziekteverzuim (minder dan een maand), het middellange (tussen een maand en een jaar) en het lange verzuim (langer dan een jaar) stegen ook in 2024 tegenover het jaar ervoor. Het percentage van werknemers dat langer dan een maand afwezig was, steeg het sterkst. Door al die afwezigheden ging in 2024 10 procent van de werkdagen in de privésector verloren door ziekte.

Het middellange ziekteverzuim is het laagst in het Brussels Hoofdstedelijk Gewest en het hoogst in Wallonië, al is Vlaanderen aan een inhaalbeweging bezig. “De stijging is het grootst in Vlaanderen en bij de arbeidersberoepen: arbeiders zijn gemiddeld iets vaker en ook langer afwezig”, zegt Katleen Jacobs, juridisch expert bij SD Worx. Maar ook bij de bedienden ziet SD Worx een stijging. Het middellange ziekteverzuim is bij werknemers jonger dan 40 jaar het sterkst gestegen.

Dertig procent is nooit afwezig
“Hoe groter de organisatie, hoe groter het risico”, gaat Jacobs verder. “Op zes jaar tijd zien wij het totale verzuim in de privésector stijgen van 8,40 procent tot 10,30 procent: relatief gezien is dit een stijging van 23 procent. De kost is aanzienlijk.”

Het korte ziekteverzuim steeg ook tegenover 2023, maar minder dan het middellange en lange. In de laatste zes maanden van 2024 lag het kortverzuim zelfs lager dan in 2023. En ook zijn er werknemers die nooit afwezig zijn. “Dertig procent was geen enkele dag afwezig in 2024”, besluit Katleen Jacobs.

◆Left ventricular assessment by 3D-echocardiography in post-COVID-19 syndrome【THE LANCET Regional Health Americas　2025年2月13日】

Summary

Background

Although short-term outcomes of Long COVID have been described, longer-term physical and mental health outcomes of Long COVID are less well-established. This study sought to assess differences in long-term physical and mental health outcomes extending up to three years among those with current, resolved, and no Long COVID, as well as duration of Long COVID and vaccination status.

Methods

This was a prospective, multisite, study of participants with SARS-CoV-2 infection from 12/7/2020-8/29/2022, with data collected through 4/2/2024. Surveys included validated tools for physical and mental health. Data were analyzed by Long COVID status (never-had, resolved, current), Long COVID duration and vaccination status.

Findings

Of 3663 participants, 2604 (71.1%) never had Long COVID, 994 (27.1%) reported current Long COVID, and 65 (1.8%) reported resolved Long COVID. Compared to never having Long COVID, current Long COVID had lower/worse scores for Patient-Reported Outcomes Measurement Information System (PROMIS) version 29 Physical (7.8; 95% confidence interval [CI] 7.3–8.3) and Mental Health (9.4; 95% CI 8.8–10.1) and higher likelihood of moderate-to-high stress (adjusted odds ratio [aOR]: 2.0; 95% CI 1.6–2.4), moderate-to-high loneliness (aOR: 1.6; 95% CI 1.4–2.0), moderate-to-severe fatigue (aOR: 3.0; 95% CI 2.5–3.7), insufficient activity (aOR for Speedy Nutrition and Physical Activity Assessment ≤4: 0.6; 95% CI 0.5–0.7; aOR for Exercise Vital Sign ≤150 min/week: 0.7, 95% CI 0.6–1.0), and worse dyspnea (aOR: 5.0; 95% CI 4.3–5.8). Resolved Long COVID had lower scores for PROMIS Physical by 2.0 (95% CI 0.2–3.8) and Mental Health by 2.3 (95% CI 0.2–4.4) than the never-had-Long COVID cohort. Number of COVID-19 vaccinations was associated with better outcomes across all measures.

Interpretation

Among participants followed up to 3 years after initial infection, those with current Long COVID had worse physical and mental health outcomes. The majority of those with Long COVID did not resolve, with less than 2% having resolved Long COVID. The resolved Long COVID cohort had moderately worse physical and mental health compared with those never-having-Long COVID. COVID-19 vaccination was associated with better outcomes.

◆Immunological and Antigenic Signatures Associated with Chronic Illnesses after COVID-19 Vaccination【medRxiv　2025年2月18日】

Summary

COVID-19 vaccines have prevented millions of COVID-19 deaths. Yet, a small fraction of the population reports a chronic debilitating condition after COVID-19 vaccination, often referred to as post-vaccination syndrome (PVS). To explore potential pathobiological features associated with PVS, we conducted a decentralized, cross-sectional study involving 42 PVS participants and 22 healthy controls enrolled in the Yale LISTEN study. Compared with controls, PVS participants exhibited differences in immune profiles, including reduced circulating memory and effector CD4 T cells (type 1 and type 2) and an increase in TNFα+ CD8 T cells. PVS participants also had lower anti-spike antibody titers, primarily due to fewer vaccine doses. Serological evidence of recent Epstein-Barr virus (EBV) reactivation was observed more frequently in PVS participants. Further, individuals with PVS exhibited elevated levels of circulating spike protein compared to healthy controls. These findings reveal potential immune differences in individuals with PVS that merit further investigation to better understand this condition and inform future research into diagnostic and therapeutic approaches.

◆Emerging drugs for Epstein-Barr virus associated-diseases【ScienceDirect　2025年2月11日】

Abstract

Epstein-Barr virus (EBV) is the first identified oncogenic virus. It causes three types of diseases: lymphomas, carcinomas, and autoimmune diseases. It is estimated that two hundred thousand deaths are due to EBV each year. After a primary infection, EBV can remain latent lifelong. Reactivation to lytic phase can be induced by various drugs including small organic molecules, biologics, or a combination of both. In this review, we identified the most relevant results obtained with small organic compounds against Epstein-Barr virus-associated diseases. Specific treatments targeting Epstein-Barr Nuclear Antigen 1 are emerging concerning small organic molecules and showed promising results against several EBV-related malignancies.

◆Oral Cavity Serves as Long-Term COVID-19 Reservoir with Increased Periodontal and Viral Disease Risk【bioRxiv　2025年2月19日】

Abstract

Background SARS-CoV-2 infection can lead to long-term health problems affecting multiple body systems termed long COVID. Currently, limited information exists about long-term oral health manifestations in COVID-19 patients with limited healthcare access.

Methods We conducted a sequential, cross-sectional study (December 2020–March 2024) to assess how racial/ethnic differences (Black/Hispanic vs White/Asian) and health disparities affect oral and non-oral long COVID symptoms and their relationship with COVID-19 vaccination. We retrospectively reviewed patients’ oral health record from University of Illinois Chicago dental clinics before vaccination (December 2020; N=1150; Covid+/- N=575/group) and after vaccination (December 2021; N=592; Covid+/- N=292/group). Participants were recruited in two separate prospective groups of COVID-19 positive subjects (February–April 2021; pre-vaccination: N=158; January–March 2024; post-vaccination: N=171), we examined clinical indicators of oral (periodontal and salivary glands) and non-oral (neurologic) sequalae 3–6 months after initial exposure. We measured viral S protein by flow cytometry and quantified inflammatory markers, viral entry receptors, and oral viral load to correlate molecular, and cellular changes in COVID-19 positive subjects before and after vaccination.

Results Our results identified racial disparity indicating oral associated post-acute sequelae (PASC) primarily manifested as periodontal (gum) disease (COVID-19 positive: 73.1±18.9% vs COVID-19 negative: 33.1±14.3%) and correlated with higher rates of dry mouth (57.5%), taste disturbance (47%), and smell loss (20%). Vaccination reduced oral PASC in COVID-19 positive subjects; however, periodontal disease indicators persisted compared to the COVID-19 negative group. Notably, 3-6 months post-infection, while SARS-CoV-2 Spike (S) transcript was rarely detected in saliva (∼6%), its protein was commonly detected (∼70%) in the COVID-19 positive subjects indicating incomplete viral clearance. This correlates with significantly higher salivary expression of viral entry receptors (ACE2, and TRMPSS2), and inflammatory mediators (IL-6, IL-8 and MMP-8), in COVID-19 positive subjects. This finding was further supported by higher prevalence of other oral viruses including Epstein-Barr Virus (70.5%), Herpes Simplex Virus (8.1%), and Human Papillomavirus (17.5%) in COVID-19 positive subjects.

Interpretation COVID-19 history significantly correlates with severe oral health complications in predominantly Black communities, while vaccination reduced but did not eliminate these issues. The oral cavity serves as a long-term viral reservoir, and periodontal inflammation with increased oral viral presence in COVID-positive patients may increase susceptibility to oral and non-oral viral diseases and identify risk for long COVID.

◆Effect of obesity on the acute response to SARS-CoV-2 infection and development of post-acute sequelae of COVID-19 (PASC) in nonhuman primates【bioRxiv　2025年2月19日】

Abstract

Long-term adverse consequences of SARS-CoV-2 infection, termed “long COVID” or post-acute sequelae of COVID (PASC), are a major component of overall COVID-19 disease burden. Prior obesity and metabolic disease increase the severity of acute disease, but SARS-CoV-2 infection also contributes to the development of new-onset metabolic disease. Since the COVID pandemic occurred in the context of the global obesity epidemic, an important question is the extent to which pre-existing obesity modifies long-term responses to SARS-CoV-2 infection. We utilized a nonhuman primate model to compare the effects of infection with the SARS-CoV-2 delta variant in lean and obese/insulin-resistant adult male rhesus macaques over a 6-month time course. While some longitudinal responses to SARS-CoV-2 infection, including overall viral dynamics, SARS-CoV-2-specific IgG induction, cytokine profiles, and tissue persistence of viral RNA, did not appreciably differ between lean and obese animals, other responses, including neutralizing Ab dynamics, lung pathology, body weight, degree of insulin sensitivity, adipocytokine profiles, body temperature, and nighttime activity levels were significantly different in lean versus obese animals. Furthermore, several parameters in lean animals were altered following SARS-CoV-2 infection to resemble those in obese animals. Notably, persistent changes in multiple parameters were present in most animals, suggesting that PASC may be more prevalent than estimated from self-reported symptoms in human studies.

◆Spontaneous, persistent, T cell–dependent IFN-γ release in patients who progress to Long Covid【ScienceAdvances　2025年2月21日】

Abstract

After acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a proportion of patients experience persistent symptoms beyond 12 weeks, termed Long Covid. Understanding the mechanisms that cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic, and monitoring purposes are urgently required. We detected persistently high levels of interferon-γ (IFN-γ) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-γ release was CD8+ T cell–mediated and dependent on antigen presentation by CD14+ cells. Longitudinal follow-up of our study cohort showed that symptom improvement and resolution correlated with a decrease in IFN-γ production to baseline levels. Our study highlights a potential mechanism underlying Long Covid, enabling the search for biomarkers and therapeutics in patients with Long Covid.

◆JAK inhibitors remove innate immune barriers to allow viral propagation【bioRxiv　2025年2月21日】

Abstract

Janus kinase (JAK) inhibitors are small-molecule therapeutics that reduce inflammation in autoimmune and inflammatory diseases by modulating the JAK-STAT pathway. While effective in alleviating immune-mediated conditions, JAK inhibitors can impair antiviral defences by suppressing interferon (IFN) responses, potentially increasing susceptibility to viral infections. This study investigates the pro-viral mechanism of JAK inhibitors, focusing on baricitinib, across various cell lines, retinal organoids, and viral strains, including a recombinant IFN-sensitive Rift Valley fever (rRVFV), influenza A (rIAV), SARS-CoV-2 (rSARSCoV-2) reporter viruses, and wild type adenovirus (AdV). Our findings demonstrate that baricitinib suppresses transcription of IFN-stimulated genes in non-infected cells (ISGs) which is triggered by type I IFNs produced by infected cells, facilitating viral propagation. The pro-viral effects were influenced by viral load, inhibitor concentration, and structural characteristics of the compound. These results underscore the dual effects of JAK inhibitors: reducing inflammation while potentially exacerbating viral infections. Additionally, the findings highlight opportunities to leverage JAK inhibitors for viral research, vaccine production, and drug screening.

◆Acute lung injury induced by recombinant SARS-CoV-2 spike protein subunit S1 in mice【BMC Respiratory Research　2025年2月19日】

Abstract

Background

The intricacies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing acute lung injury (ALI) and modulating inflammatory factor dynamics in vivo remain poorly elucidated. The present study endeavors to explore the impact of the recombinant SARS-CoV-2 spike protein S1 subunit (S1SP) on ALI and inflammatory factor profiles in mice, aiming to uncover potential therapeutic targets and intervention strategies for the prevention and management of Coronavirus Disease 2019 (COVID-19).

Methods

To mimic COVID-19 infection, K18-hACE2 transgenic mice were intratracheally instilled with S1SP, while C57BL/6 mice were administered LPS to form a positive control group. This setup facilitated the examination of lung injury severity, inflammatory factor levels, and alterations in signaling pathways in mice mimicking COVID-19 infection. Histopathological assessment through HE staining, along with analysis of lung wet/dry ratio and ultrasound imaging, revealed severe lung injury.

Results

After molding, K18-hACE2 mice exhibited a pronounced reduction in body weight and showed more significant lung injury (P < 0.05). Notably, there was a significant elevation in vascular permeability, total protein, and total white blood cells in bronchoalveolar lavage fluid (BALF) (P < 0.05), indicative of tissue damage. Additionally, the tight junction of lung tissue was compromised (P < 0.05), accompanied by intense oxidative stress marked by decreased SOD activity and elevated MDA content (P < 0.05). Cytokine levels, including IL-6, IL-1β, TNF-α, and MIG, were significantly upregulated in both BALF and serum of S1SP + K18 mice (P < 0.05). Furthermore, S1SP prominently augmented the expression of p-p65/P65 and attenuated IκBα expression in the NF-κB signaling pathway of humanized mice (P < 0.05), corroborating a heightened inflammatory response at the tissue level (P < 0.05). Conclusion

The administration of S1SP to K18-hACE2 mice resulted in severe lung injury, enhanced vascular permeability, and compromised epithelial barrier function in vivo. This was accompanied by disruption of lung tight junctions, the manifestation of severe oxidative stress and a cytokine storm, as well as the activation of the NF-κB signaling pathway, highlighting key pathological processes underlying COVID-19-induced lung injury.

◆Assessing the effects of long-COVID on mental health in the United States: a population based study【SPRINGER NATURE　2025年2月24日】

Abstract

Background

While most individuals recover fully from COVID-19, a significant proportion of survivors experience prolonged symptoms lasting three months or more, a condition commonly referred to as long-COVID. Long-COVID conditions have been associated with reduced quality of life. By utilizing a nationally representative sample of nearly a million Americans, this study provides insights into the prevalence and impact of long-COVID on anxiety and depression in the U.S.

Methods

We utilize the Household Pulse Survey data, which provides the first population-based sample on the prevalence of long-COVID, beginning with its June 2022 wave. This survey also includes questions on respondents’ mental health status—specifically anxiety and depression. We employ a quasi-experimental difference-in-differences framework to conduct research using control groups, to predict anxiety and depression among individuals who suffered from long-COVID.

Results

Approximately 51.8% of those surveyed tested positive for COVID-19 and of these 27.3% reported suffering from long-COVID. Individuals with long-COVID were twice as likely to experience anxiety and depression relative to those with mild/asymptomatic COVID-19. Our analysis at the sub-group level revealed that younger adults and females were disproportionately affected, reporting higher rates of anxiety and depression in both the COVID-19 and long-COVID groups. Additionally, individuals with lower income and educational attainment were more likely to experience mental health challenges. Relative to the reference group (Asians), Whites, Blacks, and Hispanics exhibited significantly higher odds of anxiety and depression in both groups. Notably, long-COVID was linked to a higher incidence of depression among males, which is consistent with previous research.

Conclusion

This study fills a significant gap in the literature regarding the mental health effects of long-COVID. The findings from this study provide strong evidence of the link between long-COVID and anxiety and depression, utilizing a large nationally representative sample, and employing rigorous analysis with control groups.

◆SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx【ASM Journals　2025年2月25日】

Abstract

The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-19 comorbidities or by diet. Gut commensal bacterial HS-modifying enzymes reduce spike protein binding and infection of authentic SARS-CoV-2, suggesting that bacterial grooming of the GI mucosa may impact viral susceptibility.

◆Phase-resolved Functional Lung MRI Reveals Distinct Lung Perfusion Phenotype in Children and Adolescents with Post–COVID-19 Condition【RSNA Radiology　2025年2月25日】

Abstract

Background

Although measurable organic dysfunctions are frequently absent in pediatric patients with post–COVID-19 condition (PCC), this condition adversely affects quality of life. Free-breathing phase-resolved functional lung (PREFUL) MRI may be useful for assessing lung function in pediatric patients with PCC.

Purpose

To detect lung changes in children and adolescents with PCC compared with healthy control participants using PREFUL MRI.

Materials and Methods

In this single-center, prospective, cross-sectional study conducted between April 2022 and April 2023, children and adolescents (age ≤17 years) with PCC and age- and sex-matched healthy participants underwent MRI. Subgroup analysis was performed in participants with PCC who had cardiopulmonary symptoms. Regional ventilation, flow-volume loop correlation metric (FVL-CM), quantified perfusion, ventilation and perfusion defect percentages, and ventilation-perfusion ratios were compared between participants with PCC and controls using the Wilcoxon signed rank test. Correlation of imaging parameters with spirometry, heart rate, respiratory rate, and Bell score (fatigue severity) in participants with PCC was assessed using the Spearman rank correlation coefficient.

Results

The final study sample included 54 participants (27 participants with PCC and 27 matched control participants; median age, 15 years [IQR, 11–17 years]; 14 male participants). Twenty-one participants had cardiopulmonary symptoms. Participants with PCC had lower regional ventilation (median, 0.2 mL/mL [IQR, 0.1–0.2 mL/mL] vs 0.2 mL/mL [IQR, 0.2–0.2 mL/mL]; P = .047) and quantified perfusion (49 mL/min per 100 mL [IQR, 33–60 mL/min per 100 mL] vs 78 mL/min per 100 mL [IQR, 59–89 mL/min per 100 mL]; P < .001). Participants with PCC and cardiopulmonary symptoms had lower FVL-CMs (median, 0.99 arbitrary units [au] [IQR, 0.98–0.99 au] vs 0.99 au [IQR, 0.99–0.99 au]; P = .01) and higher ventilation defect (median, 7.6% [IQR, 4.5%–15.1%] vs 5.4% [IQR, 2.7%–7.1%]; P = .047) and perfusion defect percentage (median, 3.2% [IQR, 2.4%–4.2%] vs 2.3% [IQR, 1.8%–3.5%]; P = .02) compared with matched control participants. In participants with PCC, greater lung perfusion correlated with increased chronic fatigue severity (ρ = 0.48; P = .009) and higher ventilation-perfusion mismatch correlated with increased heart rate (ρ = 0.44; P = .02). Conclusion

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.

◆Growing Up Sick【Linked in : Royal Hansen　2025年2月26日】

“A healthy [child] wants a thousand things, a sick [child] only wants one.” – Confucius

Many of you know that my son is still battling complications from Long COVID. We are well into the 5th year of his decline which began when he was 10 years old. I use the word decline deliberately as even today, in spite of every pill and blood test, the nerve pain and the afternoons lost to dense fatigue continue to generate new forms of suffering. And while the physical dysfunction is more than enough to crush him, navigating the social and emotional loneliness in these early teenage years has become its own affliction.

I was slow to understand and believe that he was not going to suddenly recover, and even slower to realize that he would steadily get worse. As this became worryingly clear, I began to speak more openly with friends and colleagues about his current state and treatments – we had already shared with our friends and families in words and videos as much of his reality as we could (for another day, I’ll try to describe how difficult it is to convince even sympathetic individuals that this is not all “in his head”). Momentum for a change in my approach to his illness grew steadily with each “crash” that he endured. Last year, I took the first step in finding more time for him by handing over my line management responsibilities to the world-class teams and leaders here at Google . That change made possible an interim role running the corporate engineering function – the CIO to the degree Google has such a job (more on this later as I learned a lot). A new leader in that role has now joined us and as I help him ramp up, I’ll take another step towards that balance of work and support of our son.

But it is not just my son. My wife has carried the overwhelming majority of the burden. That burden takes three forms. First, she cares for his daily and hourly needs – pain management, light and temperature adjustments, meals and dietary restrictions, sleepless nights. She is the first line of support. Second, she plays the role of what I can only call chief medical coordinator. The symptoms and potential implications cross neurology, immunology, rheumatology, cardiology, GI, physical therapy and because he is a child, pediatrics which is a multiplier on each of those other fields (someone told us on this journey that in medicine, children are practically a different species). Third and finally, she spends hours on the phone and online identifying new research projects which may relate to his condition. Funding, policy advocacy, physician education all need to be done at greater scale and speed. Each of these jobs could and should be full time. I’m grateful for her devotion to our son and the many others lost in the fog of this slow moving pandemic, but she can’t do it alone.

The inverse of her intense focus on Soren is the inevitable shrinking of his own social circles. Navigating the teenage years is hard enough, but to do so with an extremely limited number and variety of contacts has become unimaginable to the point of being a categorically different adolescence. He lives most hours of the day in a dark, cold room interrupted only by the refill of his over-salted water bottle and a thrice daily battery of pills. The skills and self understanding which most of us uncomfortably forge in adolescence don’t develop without the healthy gauntlet of school, sports, neighbors.

And finally, the medical and scientific developments directed at Long COVID and other post-viral syndromes are emerging at different paces and in different sub-fields. We’re optimistic, but the complexity of the underlying conditions, and the disparate nature of the research and treatments requires an advocate to connect dots and to help prioritize the needs of our patient.

All of which has led me to find time to play a more active role in Soren and Susan’s day-to-day and hour-to-hour activities. The disease and his needs don’t wait for the evening or the weekend. My change in focus won’t magically solve the problem, but I need to be there in a variety of ways that only a father and spouse can.

I am intensely blessed with the interest and support from so many as we navigate these waters. You think at 50 that life will present challenges, but I’ve learned that your child’s unfixable and relentless physical pain and emotional anguish require more than I personally have in reserve. In particular, my colleagues at Google from all over the world and all parts of the company have demonstrated the best of humanity. They continue to connect me with researchers and others in similar situations, to express concern for Soren and his plight, and to actively support me as I make this adjustment in my focus.

Practically, I’ll remain involved in many of the same bodies of work – Security, Safety, Privacy – but as more of an individual contributor than a manager. In addition, I’ll be helping with Google’s corporate usage of AI. Safely scaling and expanding the usage of AI into more full-service Agents is critical for both Google and for companies and consumers as we all learn to use this technology to the benefit of society. All of this will contribute to the fundamentals of our AI infrastructure and tools including medical and scientific research – something I care about personally for my son but more generally for victims of poorly understood pathologies across the globe.

We live in a remarkable era of technical and scientific possibility but we need to focus our investments on these most pressing health and infrastructure challenges (thank you Demis Hassabis , James Manyika and the team at Google DeepMind ). I’m redoubling my efforts in these areas. On behalf of my son Soren and my family, I invite you to join us – we are so grateful for your continued support. There is so much more to be done.