SARS-CoV-2 と COVID-19 に関する備忘録 Vol.46

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SARS-CoV-2 と COVID-19 に関するメモ・備忘録

◆SARS-CoV-2 Infection Is Associated with an Accelerated eGFR Decline in Kidney Transplant Recipients up to Four Years Post Infection【MDPI　2025年4月25日】

Abstract

Background/Objectives: Although kidney transplant recipients (KTRs) who are immune-compromised have been shown to be at high risk of adverse acute COVID-19 outcomes (i.e., mortality and critical illness), the long-term outcomes of KTRs with a history of SARS-CoV-2 infection are unknown. We aimed to compare long-term outcomes of KTRs with and without exposure to SARS-CoV-2.
Methods: This study retrospectively evaluated 1815 KTRs in the Montefiore Health System from 4 January 2001 to 31 January 2024. The final cohorts consisted of KTRs who survived COVID-19 (n = 510) and matched KTRs without COVID-19 (n = 510, controls). Outcomes were defined as all-cause mortality and changes in estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (UPCR) from 30 days up to four years post index date. Kaplan–Meier survival analysis and Cox proportional modeling were performed for mortality. Generalized estimating equations were used to analyze changes in eGFR and UPCR across time.
Results: There was no significant group difference in long-term all-cause mortality (adjusted hazard ratio = 0.66, [0.43, 1.01] p = 0.057). eGFR in controls and COVID-19 patients before infection similarly decreased −0.98 units/year [−1.50, −0.46]. By contrast, eGFR declined at a significantly greater rate (−1.80 units/year [−2.45, −1.15]) in KTRs after COVID-19 compared to KTRs without COVID-19. This association was only seen among male and not female KTRs. COVID-19 status was not significantly associated with rate of change in UPCR or acute kidney rejection rate.
Conclusions: SARS-CoV-2 infection was associated with an accelerated decline in eGFR up to four years post infection, suggesting potential long-term implications for graft health. These findings underscore the importance of vigilant monitoring and management of kidney function post SARS-CoV-2 infection in this vulnerable population.

◆Driving under viral impairment: Linking acute SARS-CoV-2 infections to elevated car crash risks【PLOS Global Public Health　2025年4月8日】

Abstract

This study explores the linkage between acute SARS-CoV-2 and car crashes across U.S. states, correlating with COVID-19 mitigation strategies, vaccination rates, and Long COVID prevalence. This investigation analyzed aggregate COVID-19 and car crash data spanning 2020–2023, with data collection occurring between March and May 2024. Analysis was done via a Poisson regression model, adjusted for population. Key variables included vaccination status, month-specific effects relating to initial pandemic shutdowns, and Long COVID rates. Results demonstrated a significant association between acute COVID-19 infections and an increase in car crashes, independent of Long COVID status to the tune of an OR of 1.25 [1.23-1.26]. This association was observed despite varying mitigation efforts and vaccination rates across states. The study found no protective effect of vaccination against car crashes, challenging prior assumptions about the benefits of vaccination. Notably, the risk associated with COVID-19 was found to be analogous to driving impairments seen with alcohol consumption at legal limits. Findings suggest significant implications for public health policies, especially in assessing the readiness of individuals recovering from COVID-19 to engage in high-risk activities such as pilots or nuclear plant employees. Further research is necessary to establish causation and explore the exact effects of COVID-19 within the CNS affecting cognition and behavior.

◆Differential decline of SARS-CoV-2-specific antibody levels, innate and adaptive immune cells, and shift of Th1/inflammatory to Th2 serum cytokine levels long after first COVID-19【WILEY Online Library　2025年4月14日】

Abstract

Background

SARS-CoV-2 has triggered a pandemic and contributes to long-lasting morbidity. Several studies have investigated immediate cellular and humoral immune responses during acute infection. However, little is known about long-term effects of COVID-19 on the immune system.

Methods

We performed a longitudinal investigation of cellular and humoral immune parameters in 106 non-vaccinated subjects ten weeks (10 w) and ten months (10 m) after their first SARS-CoV-2 infection. Peripheral blood immune cells were analyzed by multiparametric flow cytometry, serum cytokines were examined by multiplex technology. Antibodies specific for the Spike protein (S), the receptor-binding domain (RBD) and the nucleocapsid protein (NC) were determined. All parameters measured 10 w and 10 m after infection were compared with those of a matched, noninfected control group (n = 98).

Results

Whole blood flow cytometric analyses revealed that 10 m after COVID-19, convalescent patients compared to controls had reduced absolute granulocyte, monocyte, and lymphocyte counts, involving T, B, and NK cells, in particular CD3+CD45RA+CD62L+CD31+ recent thymic emigrant T cells and non-class-switched CD19+IgD+CD27+ memory B cells. Cellular changes were associated with a reversal from Th1- to Th2-dominated serum cytokine patterns. Strong declines of NC- and S-specific antibody levels were associated with younger age (by 10.3 years, p < .01) and fewer CD3−CD56+ NK and CD19+CD27+ B memory cells. Changes of T-cell subsets at 10 m such as normalization of effector and Treg numbers, decline of RTE, and increase of central memory T cell numbers were independent of antibody decline pattern. Conclusions

COVID-19 causes long-term reduction of innate and adaptive immune cells which is associated with a Th2 serum cytokine profile. This may provide an immunological mechanism for long-term sequelae after COVID-19.


COVID-19 leads to a sustained reduction of immune cells of the myeloid and lymphoid cell lineages even 10 months after the first infection. Ten months after the first infection, S- and RBD-specific IgG responses declined below the detection limit in almost 18% and in more than 80% in subjects, respectively. Anti-NC antibodies remained positive in all subjects 10 m after the first infection. A shift towards a Th2 cytokine pattern in serum accompanied by an inversion of the IFN-γ/IL-4-ratio was found between the time point 10 weeks and 10 months after infection.Abbreviations: CD, cluster of differentiation; COVID-19, coronavirus disease 2019; IL, interleukin; IFN, interferon; NC, nucleocapsid protein; NK, natural killer; RBD, receptor binding domain; RTE, recent thymic emigrants; S, spike protein; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

◆Long-COVID Postural Tachycardia Syndrome: A deep phenotyping study【medRxiv　2025年4月29日】

Abstract

Background Postural tachycardia syndrome (POTS) has emerged as one of the most common autonomic complications of Long-COVID (LC), however disease mechanisms remain incompletely understood.

Objectives To evaluate the frequency and severity of autonomic dysfunction in a subset of carefully phenotyped, previously healthy patients with LC-POTS using a detailed protocol of autonomic, cerebrovascular, respiratory, blood, and tissue analyses.

Methods Participants in this study completed a battery of autonomic function tests including measures of sudomotor, cardiovagal, and sympathetic adrenergic function, and head-up tilt (HUT) with transcranial Doppler measures of cerebral blood flow velocity (CBFv), end-tidal CO2 (ETCO2), cerebral and skeletal muscle near-infrared spectroscopy (NIRS) and plasma catecholamines. Skin biopsy was performed at proximal and distal sites and analyzed for intraepidermal nerve fiber density (IENFD) and phosphorylated alpha-synuclein (P-Syn). Results were compared to healthy controls (HC) ≥ 3 months post-COVID infection with no lasting sequelae.

Results LC-POTS participants (n=24) exhibited a greater increase in heart rate on HUT (31.1±20.3, p=0.01), and 38% exhibited elevated upright norepinephrine levels consistent with a hyperadrenergic response. CBFv did not significantly differ between LC-POTS and HC (n=10). EtCO2 and NIRS were also similar between groups. Twenty-two percent of LC-POTS and 38% of HC had decreased IENFD on skin biopsy, while 8.7% LC-POTS had dermal P-Syn aggregation on skin biopsy, compared to none of HC.

Conclusions LC-POTS was associated with widespread autonomic dysfunction, including orthostatic tachycardia, sympathetic adrenergic hyperactivity, small fiber neuropathy, and dermal P-Syn deposition. Our findings support the concept of multiple patholophysiological mechanisms in most patients with POTS triggered by SARS-CoV-2.

Condensed Abstract POTS is a common autonomic complication of LC, however mechanisms remain incompletely understood. LC-POTS participants completed autonomic function testing with orthostatic cerebral blood flow velocity (CBFv), end-tidal CO2 (ETCO2), near-infrared spectroscopy (NIRS), plasma catecholamines and skin biopsy. Results were compared to controls with no lasting sequale of COVID. LC-POTS (n=24) exhibited a greater increase in heart rate on HUT, and 38% exhibited a hyperadrenergic response. CBFv, EtCo2,and NIRS were no different between groups.. 8.7% LC-POTS had dermal synucleln aggregation on skin biopsy. LC-POTS was associated with widespread autonomic dysfunction, including sympathetic hyperactivity, small fiber neuropathy, and dermal synuclelin deposition.

◆NZ’s Long Covid blind spot nothing short of a crisis【Newsroom : Dr Anna Brooks　2025年4月29日】

This week marks International Day of Immunology, with this year’s theme focusing on the connection between the brain and the immune system – a relationship crucial to understanding the impacts of post-acute infection syndromes like Long Covid, which is currently estimated to affect 400 million people.

Cognitive dysfunction, sensory sensitivity, and nervous system abnormalities (which I often describe as ‘auto-pilot disruption’) are hallmark symptoms of this condition, yet they remain poorly recognised. We need to deepen our understanding of how these symptoms reflect real, measurable changes in how the brain and immune system interact to develop better diagnostic and therapeutic strategies for many chronic inflammatory conditions.

In line with this growing recognition, a global consensus on Long Covid has just been published, the first to bring together clinicians, researchers, and people with lived experience from 28 countries. I represented Aotearoa New Zealand as part of the lead authorship team shaping a shared framework to better understand one of the most significant and lasting consequences of the Covid-19 pandemic.

The areas where general consensus was met include: the recognition of Long Covid as a complex, multi-system condition involving neurological, metabolic, and immune dysfunction – impacts that often present as invisible disabilities and are undetectable by routine tests; an understanding that Long Covid is an umbrella term encompassing overlapping and in some cases diagnosable conditions, each of which may require specialised care; and the acknowledgement that the long-term impacts of cumulative infections in children should be a research priority.

There was also strong consensus that healthcare workers urgently need access to education to recognise the complexity of Long Covid, and that the lack of a unified clinical definition continues to hinder diagnosis, clinical care, and research. Collectively, these findings highlight the urgent need for global investment, not just in research, clinical trials, and clinical care pathways, but also in strengthening equitable healthcare access and protecting vulnerable communities from the mounting impacts of Long Covid.

Although not a definitive guide, this paper marks the first time such a broad, interdisciplinary group has aligned on clinical, scientific, and structural approaches to Long Covid. As a researcher focused on immune dysfunction and post-infection syndromes, I see this paper as a crucial first step, a foundational framework to unify efforts, guide research priorities, and support future advances in science and care.

While Long Covid has brought overdue attention to the long-term health consequences of infections, this phenomenon is not new. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has long been recognised as a serious post-infection syndrome. Some people with Long Covid will meet the diagnostic criteria for ME/CFS, distinguished by a key symptom: an inability to tolerate even minimal physical or mental effort, reflecting a breakdown in the body’s energy systems – or more directly, ‘broken’ mitochondria.

This isn’t merely feeling tired; it is debilitating exhaustion, often described as feeling ‘poisoned’, triggered even by minor exertion such as walking a few metres, and persisting for days or weeks. Unfortunately, no diagnostic tools currently exist to detect this dysfunction, medically termed post-exertional malaise. Developing such a diagnostic tool would finally provide the objective validation that patients have been missing for decades.

Recognising post-exertional malaise is critical, not just for accurate diagnosis but to prevent harm. Pushing through physical activity can worsen the underlying energy dysfunction – a phenomenon now clearly documented in scientific literature, and a risk widely acknowledged by clinical experts.

Both Long Covid and ME/CFS are under-recognised, not because they are rare, but because clinicians lack the tools and training to adequately detect the systemic dysfunction they reflect, a gap that only investment in research and better clinician education can address. With no diagnostic tests and no established evidence-based treatments, care requires a personalised approach – guided by symptoms and impacts on daily functioning and supported by input from multiple specialties.

The paper highlights areas where research is urgently needed. This includes how the immune system, nervous system, cellular energy and metabolism, and gut microbiome may all be involved; what reinfections mean for long-term recovery; and how children are affected, not just physically, but in school and daily life. Understanding the ‘how’ and the ‘why’ these conditions occur, often without warning, is critical – not just for Covid-19, but for all infections capable of triggering long-term health harms.

The global consensus paper signals emerging international scientific alignment on Long Covid and highlights the research and care gaps that demand urgent attention. What we need now is targeted research and a strategy to disseminate and educate our healthcare workforce – so we can develop the tools needed to prevent, diagnose, and care for people effectively. This consensus marks an essential starting point for action.

After all, post-infection syndromes are not new – but pandemic-scale waves of a novel virus exposed just how ill-prepared we were to recognise and respond to them. Covid-19 continues to drive long-term illness, and if we fail to invest in research and recognition now, the burden will only deepen. We must act urgently – not only to prepare for future pandemics, but to confront the growing crisis we are already facing.

◆‘Paediatricians, GPs, and schools don’t understand childhood long covid’【Irish Examiner : Helen O’Callaghan　2025年4月29日】

Jack Lambert, consultant in infectious diseases at the Mater, Rotunda, and University College Dublin, recalls seeing “long covid coming” in March 2020.

Researching the SARS and MERS viruses, he found that some people — infected a decade or two earlier —were still sick years later. “I set up a long-covid clinic in summer 2020. I started seeing adults then, and adolescents were arriving by early 2021. I started seeing some children — under-12s — in 2022, 2023.”

Lambert, a consultant in paediatric infectious disease at Great Ormond Children’s Hospital for six years, before arriving in Dublin in 2005, started seeing children and adolescents at the long-covid clinic out of necessity.

“Families were going to GPs, trying to be seen by paediatric infectious disease clinics,” Lambert says. “They were being declined; these clinics don’t see long-covid cases.

“Since the start, I’ve seen a couple of dozen children: Fewer than 20 under-12s, about 50 adolescents. But covid is still around, cases continue to accumulate. And [as a private clinic], I’m only seeing those who can afford it. Lots of families don’t have the resources.”

Between 5% and 10% of children and adolescents who get covid develop long covid. To the best of Lambert’s understanding, no dedicated long-covid paediatric service exists in Ireland. Young patients are frequently told by medics to ‘just exercise’, or ‘push through it’, or ‘give it time and you’ll get better’.

“Children who used to be athletes, who used to run around for hours a day, now they’re barely able to walk to school,” Lambert says, yet recommendations to ‘push through’ represent “the worst advice”.

“Conditions like long covid are energy-limiting. Children with long covid suffer post-exertional malaise: When they try to push too far, they crash. Their symptoms flare up. They’re totally exhausted; end up having to go to bed.”

Children are more likely than adults to be told to get on with it. “Very often, children’s symptoms are attributed to behavioural problems, to ‘faking it’. They’re made to believe it’s ‘all psychological’, not a ‘real’ physical condition.”

Long covid is associated with 300 symptoms and each sufferer typically has 10 or 15. Common symptoms include: Exhaustion, brain fog, cognitive problems, palpitations, autonomic dysregulation, energy depletion, neuro-inflammation and mood problems, headaches, and sleep disturbance.

Lambert says: “Children, adolescents, can just get exhausted looking at a computer. They are sensitive to noise, sound, and light. And they’re told, ‘You’re just anxious’. They’re not: They have autonomic dysregulation. Their para-sympathetic nervous system is imbalanced, so they’re on edge. This is adrenalin-driven rather than psychologically-driven.”

Paediatricians, GPs, and schools don’t understand childhood long covid, Lambert says. He sees “no effort” by the HSE to educate about it. “So how can GPs or schools know about it?”

The ‘flu’ for four years

Wicklow-based Christina Doyle’s three children have had seven confirmed covid infections between them. Conor, 18, and Holly, 15, were diagnosed in December 2023. By then, they had suffered debilitating symptoms, and many medics had dismissed Doyle’s concerns.

In March 2020, Conor was one of the first locally to be diagnosed with covid. Doyle says: “I knew within weeks this was something serious. He could barely leave his bed, except to go to the toilet or to vomit. He had serious nose bleeds, 20 minutes long, huge clots of blood. His joints burned like fire.

“Profound fatigue continued. It meant if he made it downstairs, he’d have to lie on the couch; he couldn’t stand for more than a minute. He was sleeping 18 hours a day.”

Holly also had joint burning sensations, as well as severe migraine, which she’d never had before covid.

“She was very rarely sick before. She doesn’t complain, so I knew there was something seriously wrong. She was crying, saying, ‘Are we ever going to get better?’

“Her main symptoms were fatigue and muscle weakness. She’d always been very active, bubbly. Now, she needed to sleep during the day. I’d say to doctors, nurses, ‘They still aren’t better’. I was told it’s a new virus, the children are just anxious.

“I remember sitting in my living room, the two of them in bed, thinking, ‘They’re both sick and nobody’s listening’.”

Mother of three Natalie Kilbane says her 15-year-old son and 13-year-old daughter never recovered after their first covid infection in October 2020. “They hadn’t been to a GP in five years. They were very active, healthy, happy kids, with no underlying issues. Our whole family is very active: We all played sports, went kayaking, hiking.”

At first, Kilbane expected their complete recovery. “It’s the narrative we were told back then: Children don’t get very sick from covid.”

Instead, she saw them suffer from severe headaches, dizziness, difficulty standing, joint pain, noise and light intolerance, intermittent sore throat, nausea, and abdominal pain for years. “It’s like they’ve had flu every day for four and a half years.”

At A&E, they had the standard blood, pulse, and temperature checks. “They were all fine. There was nothing they could do. Yet my son couldn’t sleep, lie down; he was in so much pain with headaches. My daughter’s racing heart meant she had to hold on to the wall as she walked.”

Nobody seemed able to help: A private paediatric consultant discharged them after one visit. A request for referral to an infectious disease consultant yielded nothing, because “they didn’t treat long covid”. The GP referred them to the public system.

“We waited months. It seemed to us that the public system had little understanding that long covid is a multi-system disease. We felt they weren’t keeping pace with international trials and treatments,” says Kilbane.

She gave up her job as a nurse to care for her children. Both were recently diagnosed with long covid. “They’re starting to get a little more stable. On a good day, they go to school for two hours. They’re resilient, happy kids. They love school; it’s where they see their friends. They just want normality.”

Sick and stigmatised

Lambert says long-covid symptoms can be improved.

“Teach pacing rather than pushing, only doing in the day what their energy allows. Breathing exercises and meditative techniques help retrain their parasympathetic system. Melatonin helps regulate sleep.

“Low-dose Naltrexone — shown in seven pilot studies, including an Irish one, to help 80% of patients — improves brain inflammation and immune dysregulation.”

Having her children diagnosed with long covid meant “relief, validation, finally somebody listening to me, to the children”, says Doyle. Things are looking brighter now. Since being diagnosed, practices such as “learning their limits, knowing when to stop and rest” have helped, as have medications.

Asked about supports offered to children with long covid, the HSE referred to children specifically only in the following context: “Long covid in children and young people can present in many different ways. However, evidence suggests [most] children and young people recover, with symptoms improving after six months.”

Sarah O’Connell’s two children suffer from long covid. Co-founder of Long Covid Advocacy Ireland, she along with other LCAI members, is part of a HSE working group, formed last December.

One of their tasks is to review the September 2021 interim model of care for long covid.

“LCAI hopes the HSE will treat the issue with urgency. A huge amount of research on long covid has been published since 2021. This needs to be factored in to the model of care.”

O’Connell says care for under-16s with long covid is not included in the current/interim version of the model of care. “Nor are there currently any services dedicated to managing children with long covid. Discussions [about this] are ongoing within the working group.”

Meanwhile, she urges against labelling children as school-avoidant. “We’re not saying covid, long covid are the only reasons for increased school absence. But we do know significant numbers of children, affected by long covid, are missing school.”

Recalling a young patient describing his gym teacher putting his locker further away so as to ‘push him’, Lambert says. “Something equally difficult as having this condition is not having it believed.”

◆Identification of soluble biomarkers that associate with distinct manifestations of long COVID【nature immunology　2025年4月30日】

Abstract

Long coronavirus disease (COVID) is a heterogeneous clinical condition of uncertain etiology triggered by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we used ultrasensitive approaches to profile the immune system and the plasma proteome in healthy convalescent individuals and individuals with long COVID, spanning geographically independent cohorts from Sweden and the United Kingdom. Symptomatic disease was not consistently associated with quantitative differences in immune cell lineage composition or antiviral T cell immunity. Healthy convalescent individuals nonetheless exhibited higher titers of neutralizing antibodies against SARS-CoV-2 than individuals with long COVID, and extensive phenotypic analyses revealed a subtle increase in the expression of some co-inhibitory receptors, most notably PD-1 and TIM-3, among SARS-CoV-2 nonspike-specific CD8+ T cells in individuals with long COVID. We further identified a shared plasma biomarker signature of disease linking breathlessness with apoptotic inflammatory networks centered on various proteins, including CCL3, CD40, IKBKG, IL-18 and IRAK1, and dysregulated pathways associated with cell cycle progression, lung injury and platelet activation, which could potentially inform the diagnosis and treatment of long COVID.

◆Fibrin drives thromboinflammation and neuropathology in COVID-19【nature　2025年4月28日】

Abstract

Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection. Despite the clinical evidence, the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.

◆Trends in Maternal, Fetal, and Infant Mortality in the US, 2000-2023【JAMA Pediatrics　2025年4月28日】

Abstract

Importance Accurately measuring maternal mortality trends has been challenging due to changes in data collection. This work disambiguates trends from the effects of introducing the pregnancy checkbox on death certificates and also analyzes closely related fetal and infant mortality.

Objective To describe trends in maternal, fetal, and infant deaths since 2000, including the impact of the COVID-19 pandemic.

Design, Setting, and Participants A national, population-level, epidemiological, cross-sectional analysis during 2000 to 2023 was conducted as well as a staggered difference-in-differences analysis on the pregnancy checkbox, using the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database on underlying causes of death in the US to identify maternal, infant, and fetal deaths. Study population was restricted to mothers aged 15 to 44 years for all definitions of maternal mortality.

Exposures Staggered introduction of the pregnancy checkbox on death certificates across different states.

Main Outcomes and Measures Longitudinal study (2000-2023) reporting crude rates per 100 000 population for adjusted maternal mortality and per 1000 population for fetal and infant mortality at the national level and by US Census Bureau–designated main census regions, age groups, and race and ethnicity. Staggered difference-in-differences counterfactuals (1999-2023) on impact of pregnancy checkbox.

Results The introduction of the pregnancy checkbox was associated with 6.78 (95% CI, 1.47-12.09) deaths per 100 000 live births increase in reported maternal mortality, 66% (95% CI, 14%-117%) of the total increase from 2000 to 2019, with a smaller impact on maternal mortality excluding cause unspecified (adjusted maternal death rates). Adjusted maternal death rates remained consistently between 6.75 (95% CI, 5.97-7.61) to 10.24 (95% CI, 9.22-11.34) per 100 000 live births from 2000 until 2021, when it peaked at 18.86 (95% CI, 17.48-20.32); the rate dropped to 10.23 (95% CI, 9.22-11.32) in 2022. The death rates of Native American or Alaska Native women increased the most during the COVID-19 period, almost tripling from 2011 to 2019 (10.70 per 100 000 live births; 95% CI, 7.64-14.57) to the 2020 to 2022 period (27.47 per 100 000 live births; 95% CI, 18.39-39.45). The death rates of non-Hispanic Black women were highest across time—approximately triple the rate of non-Hispanic White women in each time period. Infant death rates per 1000 live births dropped from 6.93 (95% CI, 6.85-7.01) in 2000 to 5.44 (95% CI, 5.36-5.51) in 2020, increasing slightly to 2018 levels in 2021 to 2023. Fetal death rates per 1000 live births decreased from 6.28 (95% CI, 6.16-6.31) in 2005 to 5.53 (95% CI, 5.45-5.60) in 2022.

Conclusion and Relevance Using difference-in-differences analyses, results of this study reveal that the pregnancy checkbox explained much of the observed increase in maternal mortality before the COVID-19 pandemic. Nevertheless, results of this cross-sectional study suggest that, even adjusting for pregnancy checkbox effects, most groups saw increases from 2011 to 2019 to the 2020 to 2022 period, indicating that the COVID-19 pandemic led to worse outcomes. The findings demonstrate the relevance of public health emergencies to maternal health outcomes.

◆Trends in Maternal, Fetal, and Infant Mortality in the US, 2000-2023【nature : npj viruses　2025年5月1日】

Abstract

SARS-CoV-2 variants evolve to balance immune evasion and airborne transmission, yet the mechanisms remain unclear. In hamsters, first-wave, Alpha, and Delta variants transmitted efficiently via aerosols. Alpha emitted fewer viral particles than first-wave virus but compensated with a lower infectious dose (ID50). Delta exhibited higher airborne emission but required a higher ID50. A fall in airborne emission of infectious Delta virus over time after infection correlated with a decrease in its infectivity to RNA ratio in nasal wash and a decrease in contagiousness to sentinel animals. Omicron subvariants (BA.1, EG.5.1, BA.2.86, JN.1) displayed varying levels of airborne transmissibility, partially correlated with airborne emissions. Mutations in the non-spike genes contributed to reduced airborne transmissibility, since recombinant viruses with spike genes of BA.1 or JN.1 and non-spike genes from first-wave virus are more efficiently transmitted between hamsters. These findings reveal distinct viral strategies for maintaining airborne transmission. Early assessment of ID50 and aerosolized viral load may help predict transmissibility of emerging variants.