オミクロン株が主流になってからLongCOVIDの発生率が以前よりも上昇している

プレプリント論文を機械翻訳でザッと読んだかぎりでは、メインの主張はCOVID-19患者でLongCOVIDにまで陥りやすくなる主な要因にはどういったものがあるか?ということですが、ディスカッションの後半あたりで、オミクロン株登場後に感染した人はオミクロン以前の株に感染した人に比べてLongCOVIDを発症する確率が72%→76%に上昇したということがサラッと書かれてます。

ただし、オミクロン株の登場と度重なる変異でCOVID-19患者が爆発的に増加したことを考慮すると、LongCOVID発症の確率は4%よりももっと多いと推測するのが妥当な気がします。

 

Defining the Subtypes of Long COVID and Risk Factors for Prolonged Disease
【medrxiv 2023年5月19日】

Abstract

Importance There have been over 759 million confirmed cases of COVID-19 worldwide. A significant portion of these infections will lead to long COVID and its attendant morbidities and costs.

Objective To empirically derive a long COVID case definition consisting of significantly increased signs, symptoms, and diagnoses to support clinical, public health, research, and policy initiatives related to the pandemic.

Design Case-Crossover Population-based study.

Setting Veterans Affairs (VA) medical centers across the United States between January 1, 2020 and August 18, 2022.

Participants 367,148 individuals with positive COVID-19 tests and preexisting ICD-10-CM codes recorded in the VA electronic health record were enrolled.

Trigger SARS-CoV-2 infection documented by positive laboratory test.

Case Window One to seven months following positive COVID testing.

Main Outcomes and Measures We defined signs, symptoms, and diagnoses as being associated with long COVID if they had a novel case frequency of >= 1:1000 and they were significantly increased in our entire cohort after a positive COVID test when compared to case frequencies before COVID testing. We present odds ratios with confidence intervals for long COVID signs, symptoms, and diagnoses, organized by ICD-10-CM functional groups and medical specialty. We used our definition to assess long COVID risk based upon a patient’s demographics, Elixhauser score, vaccination status, and COVID disease severity.

Results We developed a long COVID definition consisting of 323 ICD-10-CM diagnosis codes grouped into 143 ICD-10-CM functional groups that were significantly increased in our 367,148 patient post-COVID population. We define seventeen medical-specialty long COVID subtypes such as cardiology long COVID. COVID-19 positive patients developed signs, symptoms, or diagnoses included in our long COVID definition at a proportion of at least 59.7% (based on all COVID positive patients). Patients with more severe cases of COVID-19 and multiple comorbidities were more likely to develop long COVID.

Conclusions and Relevance An actionable, empirical definition for long COVID can help clinicians screen for and diagnose long COVID, allowing identified patients to be admitted into appropriate monitoring and treatment programs. An actionable long COVID definition can also support public health, research and policy initiatives. COVID patients with low oxygen saturation levels or multiple co-morbidities should be preferentially watched for the development of long COVID.

Long COVID – Current Knowledge Base and Need

Numerous symptoms are cited as long-term sequela of COVID-19. “The symptoms may affect a number of organ systems, occur in diverse patterns, and frequently get worse after physical or mental activity.”A 2020 study found that the most common long-term symptoms were fatigue, dyspnea, joint pain, and chest pain. Others reported gastrointestinal tract disorders correlated with gut microbiome shifts after COVID-19 infection. Cognitive dysfunction, often referred to as brain fog, is a commonly reported long-term symptom. Cognitive dysfunction is particularly concerning given evidence that COVID-19 can alter brain structure. The most common self-reported symptoms documented via a smartphone app were fatigue, headache, dyspnea, and anosmia.

Concerningly high long COVID frequencies have been reported. A cohort study from the Netherlands found that approximately one in eight COVID-19 patients developed long-term somatic symptoms. Another study showed that approximately thirty percent of their cohort reported persistent symptoms, with many experiencing worse health-related quality of life (HRQoL) compared with baseline and negative impacts on at least one activity of daily living.

Long COVID’s impacts extend beyond individual morbidity to include healthcare system and economic consequences. Cutler et. al. noted long COVID resulting in reduced workforce participation (e.g., 44% out of the work force), direct earning losses and worker shortages in service jobs. A recent analysis of New York State disability claims trends described in the New York Times found that “71 percent of claimants with long COVID needed continuing medical treatment or were unable to work for six months or more” and opined that long COVID has exacerbated the current US labor shortage.

The widespread occurrence of lingering ailments and their impacts on individuals and society make clear the need for a long COVID definition. U.S. public health officials note that we must balance our need for an accurate long COVID definition that includes all afflicted individuals with against our need for interim long COVID definitions to expedite immediate action and mobilization. In particular, a working definition of long COVID based on routinely collected coded data could support the identification of at risk or undiagnosed patients for monitoring, referral, or therapeutic interventions. In the current study we empirically derive an actionable broad-based long COVID definition to support current clinical, public health, research and policy initiatives related to the pandemic.

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Discussion

Numerous reports document specialty-specific signs, symptoms and diagnoses correlated with long COVID. We present a novel analysis based on a large national data set and the full multispecialty breadth of ICD-10-CM diagnosis codes to create an overall holistic long COVID definition that confirms and extends previous reports.

We allowed patients to be their own controls and used the entire cohort before and after COVID-19 infection to determine the relative risk of signs, symptoms, and disorders. This ensured that the signal was both novel and upregulated. We found COVID-19 positive patients developed signs, symptoms, or diagnoses included in our long COVID definition at a proportion of between 59.7% (percentage based on COVID positive patients tested at the VA) and 76.6% (percentage based on all COVID positive patients with diagnostic history and follow up diagnoses one to seven months after test). More than three-fourths of long COVID patients met our long COVID definition within four months of their positive COVID-19 test.

We found long COVID frequency differences based on race and ethnicity. These differences may be related to socioeconomic status, which is directly correlated with the presence of comorbidities. The long COVID cohort was eight years older with more comorbidities (two-year Elixhauser score 7.97 in the long Covid patients vs 4.21 in the non-long Covid patients). In our cohort, the males were significantly older than the females on average, 60.29 (95% CI: 95% CI: 60.24 – 60.35) versus 47.85 (95% CI: 47.73 – 47.97), respectively. We found that long COVID frequency was increased in female patients, the more severely ill, and patients who had a more severe bout of COVID as judged by their minimum oxygen saturation.

We found 143 upregulated diagnostic groups, with odds ratios as high as 23. We also found seventeen upregulated medical specialty groupings containing between three and twenty-one signs, symptoms, or diagnoses. This provides strong evidence for a broad definition of long COVID.

Carfi et al. found that most common long-term symptoms were fatigue, dyspnea, joint pain, and chest pain. Each except joint pain is represented in our long COVID definition. However, joint pain may be related to findings in our definition such as difficulty walking and an overall decrease in mobility. COVID-19 is known to cause lung abnormalities, especially in cases with pneumonia. We found that the likelihood of developing pneumonia after COVID-19 infection is significantly upregulated, potentially interconnected with the numerous findings in our Pulmonary long COVID definition. Autopsy evaluation of COVID-19 victims’ lung tissue demonstrated diffuse alveolar damage with perivascular T-cell infiltration and severe endothelial injury. Long COVID patients have been found to have abnormal Xe MRI gas exchange and CT vascular density measurements, which we postulate could be related to the pulmonary fibrosis (J84.10) or emphysema (J43.9) diagnoses identified in our definition.

Our definition shows that the long-term effects of COVID-19 are associated with damage to numerous body systems including the kidneys, heart, eyes, and nervous system. Our results are corroborated by other studies. Cognitive dysfunction (brain fog) is often associated with long COVID and can be difficult to diagnose and treat. COVID-19 infection is far more likely to cause cardiac complications than vaccination. The gastrointestinal codes we observed reflect previous literature and may relate to reported alterations to the gastrointestinal tract after COVID-19. Finally, previous studies have noted that COVID can alter ocular physiology, supporting our ophthalmology related findings.

Patients with more severe cases of COVID 19, as manifest by low oxygen saturations, should be watched carefully for the development of long COVID as they were significantly more likely to develop long COVID. Sicker patients with higher 2-year Elixhauser scores were significantly more likely to develop long COVID. Patients with multiple comorbidities should be made aware of this risk and participate in active surveillance for the development of signs and symptoms of long COVID.

The American Medical Association (AMA) notes there are three categories of long COVID patients: Those who do not recover completely and have ongoing symptoms; those with symptoms related to chronic hospitalization; and those who develop new symptoms after recovery. In our study, we did not differentiate by these subtypes and instead leave that to future research. It is possible that some of these signs and symptoms may have occurred during the first month and may be the persistent subtype. It is possible that some of the upregulated codes may be found with other serious illnesses, though only 9.1% of our cohort had severe COVID based on oxygen saturation <94%. We are not able to distinguish conditions that represent acceleration of pre-existing disease from those that represent de novo COVID-related conditions. For example, is the increased incidence of Non-ST elevation (NSTEMI) myocardial infarction (I21.4) related to the general stress of acute illness impacting preexisting coronary artery disease or to an underlying de novo long COVID related condition? Better understanding will require additional research. In any event, whether causal or associative, de novo disease or exacerbation of chronic disease, new or persistent clinical problems require assessment, treatment, and monitoring. Limitations include that the cohort study population is 84% male, reflective of the overall VA patient population which is between 87% and 95% male (depending upon data source and whether gender has been self-reported). Additionally, the male Veteran population who use the VA healthcare system is older than the population of female Veterans who use VA. Our study did not include home testing for Covid-19 that went unreported to the VA healthcare system. Patients who tested positive during the omicron dominant time period were slightly more likely to develop Long COVID when compared to the earlier strains (76% vs 72%, p<0.001). The reality of emerging viral variants emphasizes the need for a well-defined and well-maintained definition of long COVID over time and with variant-specific derivation. The study was not powered to show independence of the individual risk factors for long COVID. In this case-crossover study, we hope that our empirically defined long COVID definition will lead to more consistent identification of long COVID and its medical specialty subtypes and support of a variety of COVID related initiatives. Our definition is actionable as individuals who have multiple co-morbidities and more severe bouts of COVID should be followed more closely for the development of long covid signs or symptoms. Our definition can also inform screening questions for high-risk patients. For example, helping clinicians identify patients with enhanced long COVID risk who may benefit from monitoring programs or patients with previously undiagnosed long COVID for whom it may be appropriate to create a referral to a long COVID clinic. We also anticipate that our long COVID definition may support through standardization of future subspecialty specific long COVID research. Future research should look at health outcomes for each long COVID medical specialty subtypes to identify those at greatest risk of developing severe morbidity. Predictive analytics should be employed to help refer these individuals earlier to monitoring and treatment programs. As of March 5th, 2023, there have been 759 million confirmed cases of COVID-19 worldwide. Case counts are ever increasing. As Dr. Levine notes, immediately useful long COVID definitions are needed as are ultimately more fully inclusive definitions. We offer our long COVID definition as a public health contribution to our pandemic response.

 

Long Covid Is Keeping Significant Numbers of People Out of Work, Study Finds
【ニューヨーク・タイムズ:Pam Belluck 2023年1月24日】

Long Covid is having a significant effect on America’s work force, preventing substantial numbers of people from going back to work while others continue needing medical care long after returning to their jobs, according to a new analysis of workers’ compensation claims in New York State.

The study, published Tuesday by New York’s largest workers’ compensation insurer, found that during the first two years of the pandemic, about 71 percent of people the fund classified as experiencing long Covid either required continuing medical treatment or were unable to work for six months or more. More than a year after contracting the coronavirus, 18 percent of long Covid patients had still not returned to work, more than three-fourths of them younger than 60, the analysis found.

“Long Covid has harmed the work force,” said the report, by the New York State Insurance Fund, a state agency financed by employer-paid premiums. The findings, it added, “highlight long Covid as an underappreciated yet important reason for the many unfilled jobs and declining labor participation rate in the economy, and they presage a possible reduction in productivity as employers feel the strains of an increasingly sick work force.”

The report, which analyzed Covid-related claims from patients exposed to the virus at work, filed between Jan. 1, 2020, and March 31, 2022, and paid by the agency, provides a snapshot of the problem. The agency, one of the 10 largest workers’ compensation insurers in the country, found that nearly a third of 3,139 Covid-related claims it paid met its definition of long Covid.

Patients received coverage from the fund if they had a positive coronavirus test and the agency or a workers’ compensation board determined that they had a high risk of having been exposed to the virus while at work, typically in environments like hospitals, grocery stores or transit systems. The report classified a case as long Covid if, after infection, a patient required medical treatment for 60 days or more or lost 60 or more days of work.

“It’s a pretty conservative estimate,” said Gaurav Vasisht, executive director and chief executive officer of the insurance fund. “It’s not capturing people who may have gone back to work and didn’t seek medical attention and may still be suffering, so you know, they’re just toughing it out.”

During the time frame of the report, claims for the 977 people the fund designated as having long Covid cost about $17 million out of the approximately $20 million paid to all Covid patients, officials said, adding that the proportion for lost wages was slightly greater than for medical treatment. But Mr. Vasisht cautioned that the dollar amounts provided only a partial picture because it was unclear how long people would need medical care or time off for long Covid.

He added that the cost to patients went beyond money. “The longer you’re out of work, the harder it is for you to get back to work, and that can stigmatize patients,” Mr. Vasisht said. “It could be highly disruptive to their family and professional lives.”

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Long Covid is defined by public health authorities as a constellation of symptoms that linger after the initial infection or that emerge weeks later and can include breathing problems, fatigue and brain fog. The Government Accountability Office estimated that long Covid has affected 7.7 million to 23 million people in the United States.

Katie Bach, a nonresident senior fellow at the Brookings Institution who was not involved in the report, said the study showed that “we have a group of people who got long Covid and at least up until now have been unable to get back to work, and it is a nontrivial number of people.”

She said the report reflects only a slice of the work force: employees with workplace exposure to the virus who are knowledgeable enough about workers’ compensation to file claims. It might include employees who are younger or sicker than the overall working population, while also missing other workers with long Covid, said Ms. Bach, whose own research suggests that about 500,000 people in the United States are currently not working because of long Covid.

The New York report also found some optimistic signals. Since the pandemic’s first wave in early 2020, long Covid cases decreased as a percentage of workers’ compensations claims and of Covid-related claims. The decrease coincided with the advent of vaccines, which studies suggest reduce the risk of long Covid, and with new coronavirus treatments, supporting the idea that if people can avoid becoming severely ill from their initial infection, they are less likely to experience long-term symptoms.

Still, Mr. Vasisht said the agency continued to receive claims for workers with long Covid, especially after surges in infections. The report also suggested that more employees than reflected in the data might have met the criteria for long Covid claims. The vast majority of all Covid-related claims, over 83 percent, were filed by essential workers — in occupations like health care, law enforcement and security services. But only 29 percent of their claims met the definition for long Covid, while 44 percent of nonessential workers met that definition.

That could be because “essential workers might not have been able to stay home from work beyond the required quarantine period,” the report said. And health care workers might have “self-treated their symptoms” rather than seeking medical care, the report said, adding “essential workers may have long Covid rates higher than the data suggests, creating a blind spot for policymakers.”

“A lot of people can’t afford to not work and so they’re working when they really shouldn’t be, continuing to work while they’re sick,” said Ms. Bach. She said that the experience of people with similar post-viral conditions like myalgic encephalomyelitis and chronic fatigue syndrome suggests that some people who work despite their long Covid may have harder recoveries. “When people who have a condition whose hallmark symptoms are fatigue and brain fog go into work, they’re not going to be as productive and they’re probably reducing their odds of improvement,” she said.

And because 40 percent of claimants with long Covid returned to work within 60 days of becoming infected while still receiving medical treatment, Mr. Vasisht said, employers might receive “more requests for reduced hours or other accommodations.”

The study also found that doctors used a specific long Covid diagnostic code in only 30 cases, even though the code was added to the International Classification of Diseases in October 2021. “Physicians are underutilizing the I.C.D. code,” said Mr. Vasisht, adding that he believed his organization “can do a lot of good by conducting outreach to the physician community and letting them know about the research on long Covid and also about the existence of this I.C.D. code.”

Other findings were consistent with previously identified long Covid patterns, including results of two 2022 studies that analyzed different workers’ compensation data sets. The most common long Covid symptoms included shortness of breath, fatigue, weakness, and cognitive and memory problems.

Women appeared to be at greater risk than men, as were people who became sick enough from their initial infection to be hospitalized and those with previous conditions like lung disease, hypertension, obesity and depression. Adults older than 60 were less likely to resume working than younger employees, which might indicate that some long Covid patients are retiring early, adding to labor shortages, Ms. Bach said.

Overall, said David Cutler, an economics professor at Harvard who has researched the cost of long Covid and was not involved in the study, “the report shows that even if Covid deaths are down, Covid is not over, and it won’t be for some time.”