Category: Covid-19

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The impact of COVID-19 on the diagnosis and treatment of HCC: analysis of a nationwide registry for advanced liver … – Nature.com

February 5, 2024

Study design and participants

In this study, we retrieved data of patients initially diagnosed with HCC between January 2018 and December 2021 from the REAL database12. The collected data included anthropometric parameters, viral hepatitis parameters, antiviral treatment history before each admission, hepatic encephalopathy status, ascites, esophageal and gastric varices, tumor characteristics, treatment modalities for PLC and DC, and laboratory data (total bilirubin, serum albumin, serum creatinine, platelet count, and prothrombin time)12. We intended to enroll as many patients as possible; only those with missing information on the initial treatment were excluded.

The study was conducted in accordance with the principles of the Declaration of Helsinki. This study complied with the ethical guidelines for medical and health research involving human subjects established by the Japanese Ministry of Education, Culture, Sports, Science, and Technology and the Ministry of Health, Labour, and Welfare. The study protocol was approved by the Research Ethics Committee of the Faculty of Medicine at the University of Tokyo (approval number: 2018053NI). The requirement for individual informed consent was waived by the Research Ethics Committee of the Faculty of Medicine at the University of Tokyo due to the retrospective design of the study. All personal information was anonymized at data entry and an individual identifier was created with a hash function using the patients names and birth dates. The study was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000035000). All authors had access to the study data and reviewed and approved the final manuscript.

We classified the patients into four etiologies: hepatitis B virus (HBV), hepatitis C virus (HCV), coinfection with HBV and HCV, and non-B, non-C12. Patients were classified as HBV-positive if they were positive for HBs antigen at least once at initial diagnosis or at any admission. Furthermore, patients were classified as having HBV infection if they had a history of receiving antiviral therapy for HBV. Patients were classified as having HCV if they had a positive HCV antibody result at initial diagnosis or at any admission. Furthermore, patients were classified as having HCV infection if they had a history of receiving antiviral therapy. Patients coinfected with HBV and HCV met the criteria for both HBV and HCV infections. The remaining patients were classified as non-B, non-C12.

PLC were classified based on the World Health Organization (WHO) classification of Tumours of the Digestive System13. HCC was diagnosed pathologically or using imaging criteria based on the Japanese Clinical Practice Guidelines14. Hyperattenuation during the arterial phase with washout during the late phase on dynamic computed tomography or dynamic magnetic resonance imaging images was considered a specific finding.

COVID-19 was first documented in December 201915 and the WHO declared the COVID-19 outbreak as a global pandemic on March 11, 2020. The study period was divided into the pre-COVID-19 era (January 2018 to December 2019) and the COVID-19 era (January 2020 to December 2021).

Among the various indicators of tumor characteristics, we selected tumor size, the most robust and reliable indicator of tumor growth, as the primary outcome measure. We compared the diameter of the maximal intrahepatic lesion at initial diagnosis before and during the COVID-19 era. The following variables were also assessed: number of intrahepatic tumors, vascular invasion, extrahepatic spread, tumor rupture, Barcelona Clinic Liver Cancer (BCLC) stage16, duration from diagnosis to initial treatment for HCC, etiology, ChildPugh score17, status of hepatic encephalopathy, ascites, esophageal and gastric varices, tumor characteristics, treatment modalities for HCC, anthropometric parameters, and laboratory data (total bilirubin, serum albumin, serum creatinine, platelet count, and prothrombin time). We further conducted a subgroup analysis stratified by etiology, including HBV, HCV, and non-B, non-C.

Data are presented as means and standard deviations (SD) or medians and interquartile ranges (IQR) for quantitative variables and as numbers and percentages for qualitative variables. The body mass index (BMI), ChildPugh score, and BCLC stage were calculated using the obtained data (Supplementary Fig.S1). The following unrealistic outliers were treated as missing. Height less than 100cm, weight less than 10kg, prothrombin activity less than 10%, and diameter of the maximal intrahepatic lesion greater than 30cm. BMI, ChildPugh score, and BCLC stage calculated from these values were also treated as missing.

For comparisons between before and during the COVID-19 era, for continuous variables, Welchs t-test was used to assess the statistical significance. The CochranArmitage trend test was used for statistical analyses of the change in ChildPugh class, number of intrahepatic tumors, BCLC stage, and tumor markers, and The Chi-squared test was used for other categorical variables. In this study, p<0.05 was considered statistically significant, and all tests were two-tailed. All statistical analyses were performed using the R software version 4.1 and later (R Foundation, Vienna, Austria, http://www.r-project.org/).

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Impact of the COVID-19 pandemic on the incidence and type of infections in hospitalized patients with cirrhosis: a … – Nature.com

February 5, 2024

To our knowledge, this is the first comprehensive study analyzing the impact of the COVID-19 pandemic on the incidence and type of infections in patients with cirrhosis hospitalized in a non-intensive care unit setting. The main finding of this study was the similar incidence of infections in both periods (pre-pandemic vs pandemic) although we found a trend to a lower incidence of nosocomial infections and to a higher incidence of MDRO infections during the pandemic.

During the COVID-19 pandemic, strict measures were implemented to prevent the spread of SARS-CoV-2. These measures, such as greater awareness of hand hygiene, are also recommended to prevent infections in general and MDRO infections specifically19. We could therefore have expected a decrease in the incidence of all types of non-COVID-19 infections during the pandemic, as has been reported in the general population in outpatient medical care in Germany20 and in hospitalizations in the US21.

In the present study in hospitalized patients with cirrhosis, the incidence of all infections was similar in the pandemic to that in the pre-pandemic period, but there was a trend to a decreased incidence of nosocomial infections during the pandemic. This finding is in agreement with a report from the US that evaluated nosocomial infections in cirrhotic patients admitted to the intensive care unit22, as well as a report from China that evaluated nosocomial infections in a neurosurgery unit23, and could be attributed to the measures implemented in hospitals to fight the pandemic. However, during the first and second year of the COVID-19 pandemic, the National Healthcare Safety Network in the US described an increase in HCA infections and a high incidence in device-related infections (bloodstream, urinary tract and ventilator-associated infections)24,25. One possible explanation for these findings is that, in parallel to practices intended to prevent and control the spread of SARS-CoV-2, usual medical care was compromised due to the overall pressure on health systems: higher patient volumes and severity as well as shortages of staff and supplies. Focusing resources on SARS-CoV-2 may have reduced the attention given to traditional programs for prevention of nosocomial infections, such as venous and urinary catheter care, leading to an increase in nosocomial infections26,27.

Interestingly, as other authors have observed, we too found a (non-significant) increase in urinary tract infections during the pandemic22,23. This increase could be related to deficient urinary catheter care due to the pressure on health-care systems. We also found a non-significant decrease in SBP and lower respiratory tract infections. The latter might be explained by the measures taken to reduce contact transmission and aerosol spread23. The low rate of COVID-19 infections in our study during the pandemic can be explained by the fact that all patients diagnosed with COVID-19 were admitted to specific COVID-19 hospitalization areas. The three patients with nosocomial-acquired COVID-19 identified during the pandemic period were diagnosed during hospitalization in the hepatology department.

Like in other studies, we also found infection rates of Clostridioides difficile decreased during the COVID-19 pandemic24,25,27,28. This finding is most likely linked to the general preventive measures undertaken during the pandemicmeasures beyond the use of alcohol-based hand sanitizer to which the Clostridioides difficile spores are resistant.

Regarding MDRO infections, it is of note that although their incidence remained low (4% in the pre-pandemic and 6.5% in the pandemic group), it increased both in the community-acquired infections and the nosocomial infections during the pandemic period, as reported by Jeon et al in hospitalized patients in Korea11. In contrast, Park et al found that the rate of infections caused by MRSA and ESBL producers was significantly lower in patients with cirrhosis admitted to the intensive care unit during the pandemic. Bentivegna et al also describe a decrease in MDRO among the total numbers of infections in the general population in Rome during the pandemic10. Other authors in hospitals in Taiwan and the US have also described a reduction of MDRO among nosocomial infections during this period8,9. These contradictory findings between countries could be related to differences in antibiotic policies and/or in infection prevention measures.

We consider the low incidence of MDRO in our population in both periods is a relevant finding. Probably, the reason is that our study was performed in the hepatology unit at a hospital without liver transplant, while most of the previous studies evaluating infections by MDRO in cirrhosis were performed in an intensive-care setting and in hospitals with liver transplant program3,5,6. Therefore, it is important to emphasize the need for monitoring antimicrobial resistance at each centre to adapt the empiric antibiotic therapy. This would contribute to a more rational use of antibiotics in order to prevent further progression of antibiotic resistance.

In our study, the admission rate was statistically lower in the pandemic group. One hypothesis might be that patients chose to stay at home rather than seek medical care due to fear of exposing themselves to SARS-CoV-2 and/or to reduce the pressure on health care system. This hypothesis is further supported by the finding that liver function was more severely impaired in hospitalized patients during the pandemic. A possible reason for this could be that in view of the pandemic only the most seriously ill sought hospital care.

While some studies also report a decrease in the overall hospital admission rate for non-covid-19 conditions during the pandemic29, still others found the admission rate for alcohol-related liver events increased30,31. In our study, we observed a significant increase in the alcoholic etiology of cirrhosis during the pandemic. These data are in agreement with the increase in alcohol abuse during this period32. We observed an increase in the number of women hospitalized during the pandemic, likely related to the increase in the rate of alcohol consumption reported among women at this time and higher susceptibility to the effects of alcohol32.

The main limitation of this study is its retrospective design. Data reliability is not the same as in a prospective design in a non-pandemic situation. Second, we focused only on the two periods we considered could best show the impact of the pandemic on infections: the first year of the pandemic and the previous year. This provided a relatively low sample size that could have contributed to the lack of a statistical significance in some differences observed between the two periods. Finally, we did not include patients with cirrhosis admitted for COVID-19, so we do not have data about their eventual episodes of infection.

To conclude, we observed a trend towards a lower incidence of nosocomial infections and a higher incidence of MDRO infections during the pandemic as compared to the pre-pandemic period. Such findings indicate that even in a crisis like a pandemic, standard infection prevention practices must be maintained in order to avoid the increase of nosocomial infections and the spread of MDRO infections.

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Impact of the COVID-19 pandemic on the incidence and type of infections in hospitalized patients with cirrhosis: a ... - Nature.com

The Days Blur Together: Study Shows How the COVID-19 Pandemic Affected Perceptions of Time and Our Mental … – Baylor University

February 5, 2024

Contact:Shelby Cefaratti-Bertin, Baylor University Media & Public Relations, 254-327-8012 Follow us on Twitter:@BaylorUMedia

WACO, Texas (Feb. 2, 2023) Although time is a set duration of hours, minutes and seconds, the perception of time can vary dramatically based on the individual and especially during times of high stress and uncertainty such as disasters, recessions and most recently the COVID-19 lockdown. For example, ask anyone when a specific event occurred during the pandemic and they are likely to respond with, That happened three months ago. Or did that happen three years ago?

While there have been studies on the feeling thatthere is not enough time or experiencing time as moving too slowly, Baylor University sociologists Matthew Andersson, Ph.D., andPaul Froese, Ph.D.,investigated this sense ofmultifaceted time perceptions during the pandemic and their effects on mental well-being. Their findings using national Gallup data collected in spring 2021 in the middle of the pandemic were publishedin the journalTime & Society.

We know from existing research that people often experience time in altered ways whenever disasters strike, and we wanted to see if that was true during the pandemic as well, Andersson said.

The Baylor researchers found that Americans during the pandemic generally reported some degree of feeling rushed while also perceiving multiple types of time distortion involving slowness, quickness and days and weeks blending together. This disorientation also was frequently reported alongside other pandemic-related stressors, including economic strain, working from home, homeschooling a child and severe household conflict.

Together, they complicated how people perceive time by disrupting routines and creating experiences of trauma, adding to the decline in mental well-being and an increase in feelings of loneliness.

Time disorientation and mental well-being

The top three findings of the study all demonstrate the connection between altered time perception and the mental states of an individual.

If time does not seem to be moving normally, it is generally related to lower levels of mental well-being, such as increased depressive, anxiety symptoms or a lessened sense of control, Andersson said. We think this is because people tend to feel grounded or calm when they feel like time is moving as it should.

Secondly, the researchers found that individuals can often experience these time disorientations in multiple and contradictory ways, which can be related to even lower well-being.

Feeling rushed and feeling that time is slow are kind of opposites, but they are both related to having this sense of multifaceted blending of time, Froese said. We can show very clearly how these new stresses that were brought on by the pandemic created heightened senses of disorientation in terms of time.

More importantly, they found these time disorientations were affected by social, familial, physical andwork situations, which created lower levels of mental well-being.

Specific forms of stress we were seeing during the pandemic, such as financial hardship, homeschooling, working from home and severe household conflict, all had relationships to experiencing different kinds of time distortions, said Andersson.

This was more evident in younger people because it [lockdown] probably upended their daily routines in a much more dramatic way than it would have in somebody who's retired, said Froese.

Experience of time

The rushed pace of industrialized society existed before the COVID-19 pandemic, but the stressors associated with the pandemic added to the feelings of time being out of control.

Our approach to capturing experiences of time rests on the assumption that individuals relate to time in complex ways, Froese said. We found original evidence to suggest that experiences of quickness, being rushed, slowness and indistinct boundaries of days all coincide, and that these multiple disorientations each relate to diminished mental wellbeing, to objective work and family demands, and to widespread exposures to pandemic-related stressors.

The survey was conducted as part of the Baylor Religion Survey, one of the most extensive national surveys ofAmerican religious beliefs, values and behaviors that produces unique data concerning religion, health and community in America today. The 2021 data collection by Gallup contained a section devoted to how the pandemic affected Americans activities, including how the pandemic changed the emotional lives of Americans.

ABOUT THE AUTHORS

Matthew Andersson, Ph.D., researches health inequality as it unfolds across the life course, including educational and socioeconomic inequalities in mental and physical well-being as they relate to childhood, adolescent and adulthood factors. His work has focused on health behaviors, chronic disease epidemiology, personal social networks, informal elder caregiving, comparative parenthood, parent-child emotional bonds and public attitudes and reactions toward mental illness. His most recent book is The Science of Dignity(Oxford University Press), based on on Baylor Religion Survey data and results.

Paul Froese, Ph.D., is a professor of sociology and the director of theBaylor Religion Surveys, one of the most extensive national surveys of American religious beliefs, values and behaviors to provide the public and other researchers with unique data concerning religion, health and community in America today. The survey is fielded through a partnership with Gallup. He is the author of three books, his most recent isOn Purpose: How We Create the Meaning of Life(Oxford University Press). His research interests include the sociology of meaning, religion, comparative historical sociology, political sociology and ideology.

ABOUT BAYLOR UNIVERSITY

Baylor University is a private Christian University and a nationally ranked Research 1 institution. The University provides a vibrant campus community for more than 20,000 students by blending interdisciplinary research with an international reputation for educational excellence and a faculty commitment to teaching and scholarship. Chartered in 1845 by the Republic of Texas through the efforts of Baptist pioneers, Baylor is the oldest continually operating University in Texas. Located in Waco, Baylor welcomes students from all 50 states and more than 100 countries to study a broad range of degrees among its 12 nationally recognized academic divisions.10

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The Days Blur Together: Study Shows How the COVID-19 Pandemic Affected Perceptions of Time and Our Mental ... - Baylor University

Impact of the COVID-19 pandemic on COPD exacerbations in Japanese patients: a retrospective study | Scientific … – Nature.com

February 5, 2024

There was a decrease in COPD exacerbations in the 20202021 fiscal year compared to the 20182019 fiscal year. The difference between the two periods was the COVID-19 pandemic, and the most influential cause was the infection prevention measures including wearing masks. Medical factors other than infection control that may have reduced COPD exacerbations include improved smoking cessation rates associated with increased health motivation, treatment for COPD, and adherence to medications9. We found no significant difference in the rate of smoking cessation. Moreover, the total number of inhaled drugs, such as LAMA/LABA/ICS, which could suggest an intensification of treatment, remained almost the same. There was no apparent change in medication adherence in the medical records, at least for patients who had been continuously monitored in our department before the exacerbation. Additionally, there were reports that air pollutant concentrations have decreased during the lockdown period, associated with economic stagnation, and that the number of hospitalizations for COPD exacerbations and Asthma attacks has also decreased10,11. However, other researchers have reported that medical factors other than infection control have little impact12. Thus, because the main cause of COPD exacerbation is infection, we assumed these environmental effects including social factors remain controversial. Another factor was the reluctance to visit a doctor. There are reports of a temporary decrease in hospital visits due to the belief that hospital visits pose an infection risk following the COVID-19 pandemic13. However, in our hospital, the emergency department is mainly responsible for COVID-19 patients, and the total number of inpatients and outpatients in the respiratory department did not decrease at least, rather had a slight increase due to the expansion of the size of the practice. Additionally, patients who required systemic steroid treatment, such as those with moderate or severe symptoms, were assumed to be less likely to refrain from visiting the doctor. Hence, in this study, we considered that refraining from hospital access would have little effect on the number of COPD exacerbations. Therefore, it can be inferred that the measures taken against COVID-19 reduced the number of respiratory tract infections, which in turn reduced the incidence of COPD exacerbations.

A comparison of the patient population with COPD exacerbations before and during COVID-19 showed that patients who had exacerbations during COVID-19 had significantly lower %FEV1 and BMI. It is known that the milder the progression of COPD airway obstruction, the less frequent the exacerbations; the higher the BMI, the less likely COPD exacerbations occur14,15,16. Infection is the most common cause of the development of COPD exacerbations; however, it is not only influenced by environmental factors, including infection, but also by patient factors, such as frailty, metabolic syndrome, immune, and genetic factors17. Although no precise mechanism has been elucidated, %FEV1 and exacerbations are interrelated. The more exacerbations that occur, the more airway narrowing associated with chronic inflammation progresses. The more lung function declines, more likely exacerbations will occur due to decreased infection defense mechanisms in the patient4,18. The same was true for BMI. Although it is difficult to determine the full distribution of fat/lean body mass throughout the body, more exacerbations occur, and more muscle mass is lost with systemic inflammation. Additionally, more respiratory muscles are reduced, which can lead to more frequent exacerbations19,20.

In addition, the BODE index; B: BMI21; O: Obstruction %FEV165%; D: Dyspnea modified medical research council dyspnea scale1; E: Exercise capacity350m on a 6-min walk, which is widely known as a mortality risk assessment for COPD, can be used as a risk assessment for exacerbations21,22. The significant predictors of COPD exacerbations are low BMI, low pulmonary function, poor health-related quality of life, and a history of previous exacerbations. Moreover, %FEV1 and BMI are clinical parameters that can be obtained in daily practice, are elements with objective criteria, and play a significant role as predictors of COPD exacerbation.

Compared to patients with COPD in Western countries, Japanese patients are older, have a lower BMI (1924 vs. 2628), are more emphysema-dominant (90%), and have fewer comorbidities, such as cardiovascular disease and metabolic syndrome23,24. Nevertheless, Japanese patients have a lower frequency of exacerbations. Moreover, the exacerbation rate of COPD in Japan is low compared to other Asian countries, therefore, rather than racial disparities, universal health insurance system is thought to be the cause25. However, this study, conducted in Japan, also found that few patients had multiple exacerbations. Therefore, daily disease control may also be important in the prevention of COPD exacerbations. Additionally, regarding the possibility of random errors occurring due to sample size, the BMI data was normally distributed, and the 95% confidence interval for the population mean calculated from pre-epidemic data was 21.0923.91, unchanged from previous reports. This was similar to previous reports that exacerbation is more likely to occur with low BMI and low respiratory function which showed a significant difference even with this sample size. Although the possibility of insufficient detection of minute differences cannot be denied, it is assumed that these our result are valid.

In combination with the results of this study, it is possible that infection control measures may have been more effective in preventing exacerbations in patients with relatively infrequent COPD exacerbations, such as those with a maintained %FEV1 or above-standard BMI. We consider that patients with advanced COPD or those who are emaciated and relatively prone to COPD exacerbations might be unable to prevent respiratory infections and exacerbations even with infection control measures, resulting in a relative decline in the mean values of %FEV1 and BMI during the COVID-19 pandemic. These patients may also require further COPD exacerbation prevention that includes more thorough infection preventions and measures for unexplained exacerbations accounting for about one-third which does not rely solely on infection control.

In this study, each 2-year survey period was compared with uniform seasons to evaluate the results throughout the year and to eliminate the effects of the seasonal disparities. We found no significant difference in seasonal variation before and during COVID-19 (Fig.2). During these 4years, there were 1st-6th waves of pandemics, and the incidence in our municipality ranged from 1 to 1508 cases/100,000 persons/month, but there was also no clear correlation with the number of patients with COPD exacerbations.

Number and annual distribution of patients with COPD exacerbations before and during the COVID-19 pandemic. Distribution of the number of exacerbations per month throughout the year. No significant changes are observed in the seasonal distribution of COPD exacerbations before the COVID-19 pandemic; 20182019 fiscal year, and during the COVID-19 pandemic; 20202021 fiscal year.

Nonetheless, a limitation of this study is that it was conducted on patients treated by respiratory medicine specialists at a university hospital and did not include those treated by primary care physicians. However, the fact that most patients underwent spirometry and computed tomography at the time of COPD diagnosis is a strength of this study. Further studies should be conducted in prospective multicenter settings. In addition, because we did not exclude patients with asthma complications, it is possible that we were unable to completely exclude asthma attacks. However, the concept of Asthma and COPD Overlap has become widespread, and even after establishing a diagnosis of COPD in clinical practice, it is difficult to clearly distinguish whether asthma complications are present in many cases. From this point of view, we believe that we were able to conduct a study in line with actual clinical practice while making a more reliable diagnosis of the presence or absence of COPD.

In conclusion, during the COVID-19 pandemic, the number of COPD exacerbations decreased in both inpatient and outpatient settings. The reduction was more substantial in patients with relatively preserved %FEV1 (GOLD IIII) or in less emaciated patients (BMI20). It is suggested that infection control measures may have been effective in preventing exacerbations in COPD patients with relatively preserved BMI and lung function.

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Impact of the COVID-19 pandemic on COPD exacerbations in Japanese patients: a retrospective study | Scientific ... - Nature.com

The impact of COVID-19 fiscal spending on climate change adaptation and resilience – Nature.com

February 5, 2024

This paper used multiple methods to analyse the potential impacts of COVID-19 fiscal spending on climate change adaptation and resilience (A&R). First, we expanded an existing taxonomy of fiscal spending to incorporate A&R-relevant policy measures50. Second, we applied this taxonomy to a database of ~8,000 policies implemented by 88 countries during the pandemic and analysed the A&R characteristics of this spending. Third, we used techniques in NLP and DL to consider how A&R versus mitigation themes feature in broader policy planning in a subset of 11 countries. Figures of country spending were created using Tableau 2021.4 and tables were generated using Excel 2016.

To assess the potential impact of fiscal policy on climate change adaptation and resilience, we developed a policy taxonomy, organized around the likely impacts of fiscal archetypes on climate A&R. We developed the taxonomy by expanding the original archetype set established by the GRO50, conducting an extensive literature review, and drawing upon existing adaptation and resilience frameworks, as outlined below.

The GRO is a policy database developed by the Smith School of Enterprise and the Environment at the University of Oxford, which tracked COVID-19 fiscal policy in 88 countries from March 2020 to December 2021 (see Supplementary Table 1 for a list of all included countries)11. In the database, policies are categorized into exhaustive and mutually exclusive subarchetypes, which are each associated with one overarching archetype and designated as functioning either for rescue (that is, initial pandemic relief) or economic recovery. An additional indiscriminate archetype captures spending that does not clearly fit into specific archetypes, typically due to a lack of specificity of the policy descriptions provided by governments. Indiscriminate archetypes are classified as unclear, rather than being allocated to either the rescue or recovery phase. The original GRO included 40 archetypes and 158 subarchetypes.

Each subarchetype was assessed in ref. 11 for its potential impact on short- and long-term greenhouse gas emissions. Other potential environmental, social and economic impacts were defined for an adapted archetype set in ref. 50. Archetypes were also tagged by sector. The archetypes were developed from first principles and tested against a preliminary set of 2,000 observed policies. Archetypes were developed with a focus on fiscal policy in contractionary macroeconomic environments.

We took the GRO taxonomy and analysed the ~8,000 COVID-19 policies recorded in ref. 11 to identify gaps where policies might have A&R characteristics but were categorized to archetypes that would traditionally not be considered A&R-related. For example, while most tourism incentives (archetype S) might be considered poor for A&R, Spains US$1.62 billion initiative to improve sustainability in the tourism sector (special attention to Balearic and Canary Islands) could have positive A&R impacts, hence a new subarchetype, Incentives for tourism with A&R conditions, was introduced21.

Next, the augmented taxonomy was compared to existing adaptation and resilience frameworks, such as the IPCCs adaptation actions22 and the European Unions sustainable finance taxonomy23, to identify further gaps. Various classification approaches already exist in climate A&R scholarship; however, they operate at a coarser level. The European Unions taxonomy for sustainable economic activities uses a sectoral classification approach to account for A&R activities alongside other sustainability criteria23. The United Nations Office for Disaster Risk Reduction (UNDRR)s climate resilience classification framework follows a similar sectoral approach51. The CRAFT framework adds a level of granularity by categorizing policies according to the type of activity they represent (rather than the sector), which incorporates both cross-sectoral and sector-specific policies, resulting in 293 subarchetypes (42 archetypes), triple the 88 of the European Union taxonomy.

Existing approaches to categorizing A&R spending tend to emphasize physical adaptation actions, failing to consider the broader impacts of spending on climate resilience. The assessment framework developed by multilateral development banks for aligning activities with the Paris Agreement, for example, focuses specifically on policies that manage physical climate change risks52. More broadly, A&R frameworks tend to evaluate only actions that are explicitly oriented towards adaptation and resilience. For example, the World Bank53 proposes six priority adaptation policy actions, spanning: inclusive development; facilitating adaptation and protection against shocks for firms, peoples, land and public assets; managing economic and financial risk; and monitoring of interventions. Similarly, the UNDRRs Budget Tagging guide for Disaster Risk Reduction and Climate Change Adaptation focuses only on activities explicitly oriented towards these objectives. CRAFT, by contrast, includes policies that are explicitly targeted at climate change adaptation actions (which we classify as direct A&R), alongside policies that are not explicitly climate-oriented, but which may have positive implications for climate adaptation or resilience (identified as indirect A&R). Importantly, CRAFT adds depth to existing approaches by covering policies that improve, reduce or have no impact on A&R, rather than focusing solely on actions that explicitly aim to enhance A&R, allowing us to provide a more holistic picture of the proportion of fiscal spending with potential positive, neutral and negative impacts on climate A&R.

Through an extensive literature review, each existing and new subarchetype was assessed for its potential impact on climate A&R. Archetypes were scored using a 3-point Likert scale (negative, neutral, positive) for two dimensions: direct and indirect climate A&R. We defined direct A&R as explicit efforts to adapt to current or expected climate effects, that is, policies that aim to implement direct adaptation actions. Examples of policies with potential positive impacts on direct climate A&R include the construction of seawalls or efforts to secure coastal ecosystems by planting mangroves54,55.

We defined indirect A&R as efforts that increase resilience or reduce vulnerability to climate change effects, regardless of whether the intention was to directly address climate risks. For example, policies that build capacity for local utilities were identified as having a potential positive impact on indirect climate A&R, because utilities provide services (water supply, waste and sanitation, energy distribution) that are crucial to the functioning and adaptive capacity of individuals, communities and systems24. Similarly, spending on education, even that which is not climate-specific, has been found to increase adaptive capacity and thus was scored positively for indirect climate A&R56,57. Healthcare systems are also crucial to ensuring the ability of populations to adapt and be resilient in the face of climate change58. Other policies that have expected positive impacts for indirect climate A&R include capacity building for subnational public entities, supply chain resilience measures, increasing social and political inclusion, enhancing managerial capacity, and providing access to institutions and information59.

All subarchetypes with a positive direct impact also have a positive indirect impact. This is because specific adaptation actions have broader impacts for climate change adaptation and resilience. For example, the construction of a seawall is also expected to enhance the economic resilience of coastal communities, hence this subarchetype, which was scored positively for direct A&R, was also scored positively for indirect A&R. By contrast, not all policies that were scored positively for indirect A&R were scored positively for direct A&R. For example, education investment that did not specify adaptation or resilience measures was not scored positively for direct A&R, even though it has a positive impact on indirect A&R by enhancing adaptive capacity more broadly. By scoring policies for both direct and indirect A&R impacts, we recognize that climate A&R extends beyond physical adaptation actions and intersects with social, political, economic and environmental resilience60,61. Supplementary Table 9 outlines all policy archetypes with a positive score for either direct or indirect climate A&R, while a literature review and justification for each score is provided in ref. 20.

Policy archetypes that are not expected to have a positive impact on direct or indirect A&R were treated in two ways. Policies that have little relevance to climate A&R were scored as neutral (0). For example, general tax cuts and interest rate reductions do not contribute to direct climate adaptation, and their short-term nature means that any savings they create for individuals or businesses do not contribute to climate resilience by building adaptive capacity. Some policies were scored as neutral for climate A&R because their impacts are limited to the COVID-19 pandemic. For instance, the provision of basic needs (shelter, food, social services), if secured beyond the pandemic, would contribute to adaptive capacity. However, short-term provision of basic needs, delimited to the pandemic, were scored as having a neutral climate A&R impact.

By contrast, policies that entail lock in of non-resilient infrastructure or promote maladaptation were scored as having a negative climate A&R impact. For example, spending on general transportation, energy and urban development infrastructure without regard to resilience is likely to result in lock in, whereby assets with long lifespans are maladapted to changing and uncertain local climate conditions26. There are a few exceptions, whereby infrastructural policies that are non-resilient are counterbalanced by the positive adaptation and resilience impacts of that archetype. For example, education and healthcare infrastructure constructed without regard for resilience may have lock-in potential; however, these impacts are counterbalanced by the adaptive capacity benefits of strengthening education and healthcare facilities, resulting in a neutral score. We did not score any liquidity policies negatively, as we do not expect this short-term funding to result in long-term infrastructure investments with lock-in potential.

Policies that are positive from a mitigation standpoint, such as the construction of renewable energy infrastructure, without consideration of infrastructure resilience, are not always positive for climate A&R. In terms of indirect A&R, clean energy infrastructure provides sustainable jobs and enhances access to energy, both of which are crucial to adaptive capacity24. However, these positive impacts are outweighed by the vulnerability of these facilities to future climate impacts if the new infrastructure is constructed without resilience in mind62,63. On balance, these policies are thus expected to have a potential negative impact on indirect climate A&R, despite their positive impact on mitigation.

We recognize the distinction in the literature among the three dimensions of resilience: absorptive capacity, adaptive capacity and transformative capacity64. However, we did not score policy archetypes for their distinct impacts on each of these dimensions. As ref. 64 highlights, specific interventions are likely to have impacts on multiple dimensions, depending on the intensity of the disturbance and the time of exposure. Policies tend to vary widely on these dimensions for any given subarchetype, such that it would appear misleading to score a policy archetype for a specific dimension.

The CRAFT framework includes 42 archetypes and 293 subarchetypes. This represents a step forward in granularity of taxonomies for assessment of adaptation and resilience impacts of policy interventions. The European Unions taxonomy for sustainable economic activities incorporates only 88 policy types, while the UNDRRs Budget Tagging guide for Disaster Risk Reduction and Climate Change Adaptation classifies activities into 20 broad areas, further broken down into 77 action areas. CRAFT therefore offers more specificity in its assessments than existing approaches. Nonetheless, a taxonomic approach can never replace the specificity of individual policy-level impact assessments; necessarily, there will be variation in the types of interventions assigned to specific categories. For example, even within the subarchetype of agricultural investment with A&R conditions, there will probably be variation in the extent of impact of individual policies that cannot be captured through our Likert-scale assessments of positive, neutral and negative direct and indirect A&R impacts. Only impact evaluations at the policy level can truly capture the potential impact of specific policies on A&R; however, this is not always feasible for policymakers or researchers. A taxonomic approach thus enables an approximate assessment that is scalable, feasible and replicable. While there is likely to be some variation in policy impacts within subarchetypes, CRAFT offers a higher level of granularity than existing assessment approaches, thus offering useful insights for policymakers and researchers alike.

The new policy taxonomy developed for assessing potential A&R impacts was applied to the GRO database11. The GRO database records all fiscal policies implemented by 88 countries over the period of March 2020 to December 2021. Each policy is assigned to a subarchetype and thus takes on the direct and indirect A&R scores, which are implemented at the subarchetype level. Policy names, descriptions, local currency amount (and US$ equivalent) and several other fields are captured for each policy, enabling aggregations at the country and archetype level.

To test the validity of the taxonomy for the GRO, we conducted a robustness check for a subset of policies per archetype. We manually reviewed 4,459 policies out of a total set of 8,037 policies to ensure a 95% confidence interval at 5% margin of error for every archetype. The sample was randomly selected per archetype, with a minimum of 10 policies selected per subarchetype (unless the subarchetype contained less than 10 policies, in which case we reviewed every policy) to ensure coverage of all subarchetypes. For each selected policy, we evaluated whether the direct and indirect A&R scores assigned at the subarchetype level fit the policy description, examining the source documents where clarification was required. We assigned a confidence rating of High where the percentage of inconsistencies in the random sample was between 010%, Medium for 1020% and Low for 20100%. We found that 97% of total spending and 96% of recovery spending were associated with archetypes with fewer than 20% scoring inconsistencies (medium to high confidence) (Extended Data Table 2). We also found that 93% of all archetypes and 94% of recovery archetypes were identified as having a medium to high confidence rating. We report our results as a range, with the lower bound referring to high and medium confidence subarchetypes only, and the upper bound including subarchetypes of all confidence levels, except where all policies are high and medium confidence, in which case only one figure is reported.

In analysing the GRO data, we also evaluated correlations between A&R spending, country income levels and the vulnerability indicators developed by the ND-GAIN32. ND-GAIN defines vulnerability as the propensity or predisposition of human societies to be negatively impacted by climate hazards32. This vulnerability index is a compound measure of exposure, sensitivity and adaptive capacity. Exposure is defined as the physical factors external to the system that contribute to vulnerability. Sensitivity is the extent to which a country is dependent upon a sector negatively affected by climate hazard, or the proportion of the population particularly susceptible to a climate change hazard. Adaptive capacity indicates the availability of social resources for sector-specific adaptation, which can include sustainable adaptation solutions32. We extracted the indicators for our 88 studied countries for the year 2020. We also extracted World Bank31 data for country income levels (GDP per capita and GNI per capita) for 2020.

To assess how A&R themes feature in broader policy planning, we first identified a set of 78 core policy papers (Supplementary Table 8) that were framed as plans for economic recovery, covering 11 of the G20 countries (that is, all those with policy documents published in English). The policy paper corpus was selected from source documents provided by the GRO, supplemented by key-term database searches to add missing budget documents. We analysed the English corpus for text related to A&R and climate mitigation using a climate dictionary expanded from previous papers with techniques in deep learning. The corpus was limited to English documents as vocabularies differ considerably across languages; we leave this exercise to be repeated by future works in other languages, but do not expect the direction of the results to change.

Creating bespoke dictionaries for NLP analysis is notoriously difficult45,65. The objective is to identify a complete set of terms that are broad enough to capture all mentions of a particular theme but precise enough to exclude irrelevant themes. One method for dictionary creation involves surveying subject matter experts, but experts are prone to missing important terms45,65,66. Supervised and active unsupervised methods both offer useful advances44,67, but previous applications struggle to fully address the limits of setting an appropriate starting dictionary. Reference 68 build on ref. 66 to demonstrate a classification approach that iteratively identifies keywords relevant to the emergent themes of a prescribed document set. In our case, where A&R is often a very minor theme in the policy documents and the corpus is small, the classification approach is unlikely to generate substantial additional terms. Instead of a classifier approach, we adopted the method of ref. 45 to iteratively expand a starting dictionary on the basis of embedding models of the target corpus itself; this is a similar method to the later work of ref. 69. The dictionary expansion process began with the full set of policy papers. From these papers, terms (words, bigrams and trigrams) were embedded using the word2vec neural network model, resulting in three separate 100-dimensional embedding spaces. In each space, every term (1:n) was combined with every other term, resulting in a total of n factorial possible term pairs. The vectorized positions of each pair were then averaged and the term closest to this average position was added to the dictionary. An initial set of vectorized A&R terms served as a starting point for this search. Once added, these new terms were manually reviewed. This procedure was iteratively performed until no additional terms emerged. Similar to the classifier approach, the method is somewhat limited by the low overall prevalence of A&R discussion in the policy paper corpus (topic model available in Supplementary Information; also see Extended Data Figs. 2 and 3).

As an alternative approach to dictionary building, we experimented with deep learning BERT70, expanding and categorizing lists of climate A&R and mitigation terms sourced from ref. 45. The transformer architecture is unique in its use of self-attention to differentially weight the significance of input data, processing an entire input simultaneously rather than sequentially. This allows for better contextual learning than previous approaches such as Recurrent Neural Networks71. BERT is the preeminent transformer model, pretrained on a corpus of 3.3 billion words to understand how English words relate to each other. It learns a target words meaning on the basis of the full sentence in which it occurs, whereas a popular alternative, Generative Pretrained Transformers, learns meaning from words that occur only earlier in a sentence than the target word. BERT has been applied to countless topics, including climate mitigation issues (see ClimateBert in the study of refs. 72,73 on electric vehicles), but not, so far as we know, to questions of climate A&R.

We used BERT to identify terms relevant to concepts of climate A&R and mitigation, supplementing language from ref. 45 and that provided by experts. To do so, we fine-tuned a BERT model using policy names and descriptions provided by the GRO dataset of ~8,000 COVID-19 fiscal policies. The model was subsequently trained to identify fiscal provisions that supported direct and indirect adaptation on the basis of policy titles and descriptions. The trained model was then applied to the policy document corpus to identify language consistent with strong climate A&R and mitigation. A subset of selected clauses was manually reviewed to identify new terms for the base dictionary. Dictionary terms were categorized into those that support adaptation, mitigation and both/unclear using the climate A&R taxonomy impact assessment matrix, CRAFT20. The full dictionary and categorizations are included in Supplementary Table 10, and Extended Data Figs. 2 and 3.

Applying the BERT-supplemented dictionaries, we used basic NLP techniques and manual sorting to categorize all 124,593 clauses in the 78 policy papers into those that pertained to topics of general climate, climate mitigation, climate A&R, other forms of A&R and other. Table 2 provides a preliminary statistical account of term usage across the policy papers. These results are helpful for direct comparisons within a country or proportional comparisons between countries. They are unsuitable for direct comparisons between countries as the typology of policy documents vary considerably. Recorded mentions of non-climate A&R are likely to underestimate usage as the dictionaries were developed to target climate topics.

Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.

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The impact of COVID-19 fiscal spending on climate change adaptation and resilience - Nature.com

Weatherhead’s Michael Goldberg shares challenges of movie theater operations post COVID-19 – The Daily | Case Western Reserve University

February 5, 2024

Coming soon: Movie theater to reopen at Great Northern Mall by early summer

WEWS:Michael Goldberg, associate professor of design and innovation at Weatherhead School of Management and executive director oftheVeale Institute for Entrepreneurship, discussed some ofthechallenges facing theater operators since COVID.

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Weatherhead's Michael Goldberg shares challenges of movie theater operations post COVID-19 - The Daily | Case Western Reserve University

At-risk patients often not offered antivirals for COVID-19, analysis shows – University of Minnesota Twin Cities

January 28, 2024

Four out of five Veterans Affairs (VA) patients who had mild COVID-19 but had compromised immune systems were not offered the use of COVID antivirals, according to a study today in Morbidity and Mortality Weekly Report.

The study, though small, illustrates the reluctance of providers to prescribe antivirals, including Paxlovid, to patients who present with mild illness, but are at risk of progressing to severe disease.

Currently in the United States, anyone age 12 and older at risk for severe progression of disease is eligible for antiviral use at the first sign of a COVID-19 diagnosis. The antiviral drugs nirmatrelvir/ritonavir (Paxlovid) and remdesivir (Veklury) are approved by the Food and Drug Administration, and molnupiravir (Lagevrio) is authorized for emergency use.

When used within 5 days of symptom development, antivirals can reduce the severity and duration of the disease. But currently reported antiviral use among the general adult population has been 35% or less.

In today's study, VA researchers reviewed 110 VA patients who were at risk for severe COVID-19 (mostly due to organ transplantation or hematologic malignancies) but did not receive an antiviral. All patients were seen between from 1, 2022 (when effective oral antivirals became widely available to treat outpatients with mild-to-moderate COVID-19) through September 30, 2022.

Among the patients, all of whom were vaccinated against COVID-19, 22 (20.0%) were offered treatment but declined, and 88 (80.0%) were not offered treatment.

Of those not offered antiviral treatment, provider reasons included symptom duration of more than 5 days (22.7%), concern about possible drug interactions (5.7%), or absence of symptoms (22.7%). For almost one half (43 of 88; 48.9%) of these patients, no reason for not offering antivirals was given other than mild symptoms. No providers mentioned Paxlovid reboundwhich might not be caused by the drug at allas a reason to not prescribe.

"These findings suggest that education of patients, providers, and medical personnel tasked with follow-up calls, combined with advance planning in the event of a positive test result, might improve the rate of recommended antiviral medication use to prevent severe COVID-19associated illness, including death," the authors concluded.

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At-risk patients often not offered antivirals for COVID-19, analysis shows - University of Minnesota Twin Cities

‘If it’s COVID, Paxlovid’? For many, it should be easier to get. Here’s what to know about antivirals – Yahoo News

January 28, 2024

The commercials make it sound so simple: "If it's COVID, Paxlovid."

But the slogan, catchy though it may be, belies a harsher reality that some public health and elected officials have long acknowledged and worked to rectify: For many, getting access to the therapeutic should be much easier than it has been.

The issue is not one of scarcity, as the antiviral is widely abundant. Nor is pricing a major barrier, as Paxlovid is cheap or even free for many. Nor even is it an issue of how well it works, as studies have shown it to be highly effective.

The drug's biggest impediment has been, and remains, the simple fact that a number of doctors are still declining to prescribe it.

Read more: Here's why some high-risk patients aren't getting drugs to combat COVID

Some healthcare providers hinge their reluctance on outdated arguments, such as the idea of "Paxlovid rebound" the chance that people who take the drug have a chance of developing COVID symptoms again, generally about two to eight days after they recover.

As it turns out, anyone who gets COVID-19 has a similar rare chance of rebound.

COVID "rebound can occur with or without [Paxlovid] treatment," scientists with the Food and Drug Administration wrote in a study published in December. "Viral RNA rebound was not restricted to [Paxlovid] recipients, and rebound rates were generally similar to those in placebo recipients."

When told about one patient who was declined a prescription to Paxlovid because of concern about "Paxlovid rebound," UC San Francisco infectious-diseases expert Dr. Peter Chin-Hong groaned.

"Oh my God, that's so, like, bogus," Chin-Hong said. "Clinicians having this weird idea about rebounds, it's just dumb."

Read more: For some COVID patients, 'Paxlovid rebound' has nothing to do with Paxlovid

Data indicate that most people don't get COVID rebound, Chin-Hong said. And while rebound can occur, the possibility should not dissuade people "who might really need it" from taking an antiviral.

Even if COVID rebound happens, and symptoms do occur, "they tend to be mild and do not require repeating the treatment," according to the California Department of Public Health.

Officials at both the federal and state level have implored healthcare providers to properly prescribe Paxlovid and other antivirals when indicated.

"Antivirals are underused," the Centers for Disease Control and Prevention said in a statement Thursday. "Don't wait for symptoms to worsen."

In its own advisory, the California Department of Public Health said, "Most adults and some children with symptomatic COVID-19 are eligible for treatments ... Providers should have a low threshold for prescribing COVID-19 therapeutics."

Read more: California has plenty of anti-COVID drugs, but doctors aren't prescribing them

Aside from Paxlovid, one alternative oral antiviral treatment is known as molnupiravir. There's also remdesivir, which is administered intravenously.

The CDC says Paxlovid and remdesivir are the preferred treatments for eligible COVID-19 patients.

"Don't delay: Treatment must be started within five to seven days of when you first develop symptoms," the CDC says.

A reference to Paxlovid and other antivirals is even in a musical radio ad from California health authorities that has been broadcast throughout the state: "Test it. Treat it. You can beat it," with the ditty later continuing: "Medication is key / To slow the virus in your body."

Yet there is wide documentation of the low frequency of prescribing Paxlovid and other antivirals, and that can have significant consequences for higher-risk COVID-19 patients. A report published by the CDC Thursday reviewed 110 COVID-19 patients considered high-risk and found that 80% of them were not offered antiviral treatment.

A big reason given by the patients' providers, all of whom were under the Veterans Health Administration, was that their patient's COVID symptoms were mild.

Read more: I have COVID-19. What to know about Paxlovid, molnupiravir, other treatments in California

But as officials note, that's exactly what antivirals are for.

"There is strong scientific evidence that antiviral treatment of persons with mild-to-moderate illness, who are at risk for severe COVID-19, reduces their risk of hospitalization and death," the CDC says.

Risk factors for severe COVID-19 include being age 50 and up; not being current on COVID vaccinations; and a wide array of medical conditions, such as diabetes, asthma, kidney disease, heart disease, having anxiety or depression, and being overweight. Other factors that influence health, such as limited access to healthcare and having a low income, can also heighten someone's risk.

Another reason providers may cite to not prescribe COVID antivirals, California officials said, is the chance of serious side effects. But that fear is largely erroneous, as "most people have little-to-no side effects," the California Department of Public Health says. Some of the more common side effects after taking Paxlovid are developing a temporary metallic taste in the mouth, which occurs in about 6% of recipients, and diarrhea (3%).

However, some people who do take Paxlovid may need to have other medications adjusted, according to the agency.

The other antiviral pill option, molnupiravir, "has very few side effects, but you cannot take it if you are pregnant," the state agency said.

Read more: California relaxes COVID isolation guidance. What you need to know

Clinicians may also be reluctant to prescribe Paxlovid for younger adults, "not because it causes harm, but because it in some studies doesn't show as much benefit," Chin-Hong said. Younger, healthy people are generally unlikely to die from COVID or become ill enough to require hospitalization even without antiviral treatment.

But some data do suggest that patients who take Paxlovid clear out coronavirus from their bodies faster.

"What we're finding is that people are turning negative very quickly with Paxlovid," Chin-Hong said.

And one report, published in the journal Emerging Infectious Diseases, suggests widespread use of Paxlovid "would not only improve outcomes in treated patients but also ... reduce risks of onward transmission."

Read more: With COVID on the rise, your at-home test may be taking longer to show a positive result

So if an initial clinician turns you down for a Paxlovid prescription, and you think you qualify, what other options are there?

One possibility is reaching out to another healthcare provider who might be either more knowledgeable about Paxlovid and other antiviral medications or more open to prescribing them.

Los Angeles County residents can call the county's public health info line, (833) 540-0473, to discuss treatment options with a health provider.

Californians who dont have insurance or have a hard time getting anti-COVID-19 medication canschedule a free telehealth appointment by calling (833) 686-5051 or visitingsesamecare.com/covidca.Medication costs may be subject to a copay, depending on your insurance.

A program funded by the National Institutes of Health, featured at test2treat.org, gives adults who test positive for COVID-19 or flu free access to telehealth care and treatment.

Sign up for Essential California for news, features and recommendations from the L.A. Times and beyond in your inbox six days a week.

This story originally appeared in Los Angeles Times.

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'If it's COVID, Paxlovid'? For many, it should be easier to get. Here's what to know about antivirals - Yahoo News

Long COVID: Study reveals potential cause of prolonged symptoms – Medical News Today

January 28, 2024

Approximately 10%-20% of individuals with a SARS-CoV-2 infection experience lingering symptoms beyond three months after symptom onset. These symptoms referred to as long COVID, can be debilitating, but there is a lack of diagnostic or therapeutic tools.

A new study published in Sciencefound that patients experiencing long COVID symptoms six months after the SARS-CoV-2 infection show dysregulation of the blood clotting or coagulation system and the complement pathway, which is a part of the immune system.

These changes in the coagulation and immune systems in long COVID patients were shown to predict the persistence of symptoms at six months. They may have the potential for the development of diagnostic tools. Moreover, therapeutics to counter the changes in the blood clotting and immune system could help alleviate long COVID symptoms.

Dr. Wolfram Ruf, Scientific Director at the Center for Thrombosis and Hemostasis (CTH), Johannes Gutenberg University, wrote in an accompanying editorial:

Although therapeutic interventions with coagulation and complement inhibitors in acute COVID-19 produced mixed results, the pathological features specific for Long Covid suggest potential interventions for clinical testing.

Long COVID refers to one or more symptoms that persist or develop after the acute phase of a SARS-CoV-2 infection. Common symptoms of long COVID include muscle weakness, fatigue, and brain fog.

Tissue damage, persistent inflammation, production of autoantibodies, and reactivation of latent virus reservoirs are some factors that have been hypothesized to cause long COVID. However, the lack of knowledge about the precise mechanisms underlying long COVID has hampered the development of diagnostic tools and targeted therapies.

Several studies have shown that individuals with long COVID show immune system dysregulation. The present study further examined changes in the immune system associated with long COVID at six months.

The study included 39 healthy participants and 113 individuals with confirmed SARS-CoV-2 infection. During the 12-month follow-up period after the onset of a SARS-CoV-2 infection, 40 out of the 113 participants with an acute SARS-CoV-2 infection had at least one persistent symptom at the 6-month follow-up visit.

Serum samples were collected from the participants during the acute phase of the infection and six months after the infection. These serum samples were used to quantify changes in more than 6,500 proteins.

The participants with long COVID symptoms at six months showed changes in serum proteins belonging to the complement system compared with healthy individuals or those without long COVID at six months. The complement system is a part of the innate immune system, which serves as the first line of defense against germs.

The complement system activation helps elicit an immune response against pathogens or damaged tissue. During the activation of the complement pathway, the plasma proteins belonging to the complement system interact with each other to form a terminal complement complex. The terminal complement complex binds to the surface of or inserts into the membrane of pathogens and damaged cells to induce cell death or promote their removal by engulfment by phagocytes.

Among patients with long COVID at six months, the researchers found increased activation of the complement pathway during acute SARS-CoV-2 infection and at six months after diagnosis. Increased activation of the complement pathway and terminal complement complex formation in 6-month long COVID patients could lead to tissue damage.

The proteins in the complement system can be activated by three distinct pathways, each involving different types of molecules. The three complement activation pathways include the classical pathway, the alternative pathway, and the lectin pathway.

Individuals with long COVID at six months showed increased expression of molecules involved in forming the terminal complement complex via the activation of the classical and alternative pathways than those without long COVID or healthy patients.

In addition to the three complement activation pathways, thrombin, a protein that promotes blood coagulation, can also cause the activation of the complement pathway and lead to the formation of the terminal complement complex.

Patients with long COVID symptoms at the 6-month follow-up showed lower levels of antithrombin III, an enzyme that inhibits thrombin, during the acute phase and at six months after the onset of a SARS-CoV-2 infection than healthy individuals. The lower antithrombin III levels were accompanied by increased expression of markers of thrombosis, a state characterized by the formation of clots in the absence of bleeding.

Patients with long COVID at six months simultaneously showed increased markers for inflammation and those for thrombosis. The cooccurrence of inflammation and thrombosis is referred to as thromboinflammation.

Signs of thromboinflammation observed in individuals with long COVID at six months included destruction of red blood cells and dysfunction of endothelial cells that line blood vessels. Moreover, these patients also showed increased markers of tissue damage in the blood.

These changes associated with thromboinflammation reflect the dysregulation of the complement system in patients with 6-month long COVID. The dysregulation of the coagulation system in long COVID patients also underscores the need for cardiovascular health assessment.

The researchers found that changes in specific complement protein levels, coagulation system biomarkers, and age and body mass index predicted long COVID at 6 and 12 months.

MNT spoke with Dr. Hrishikesh Kulkarni, Assistant Professor of Medicine at Washington University School of Medicine, who was not involved in the study. Dr. Kulkarni said:

By utilizing an unbiased screen and confirming it using distinct components of the membrane attack complex by which the complement system damages cells, the authors demonstrate that persistently increased complement activation is a key feature of Long COVID. Moreover, their models that incorporate the measurement of 2 protein ratios improve an already good clinical model comprising of age and body-mass index, most notably for 12-month Long COVID.

The classical complement pathway is activated upon antibodies binding to viral proteins or autoantibodies in the bodys tissue. In the present study, the serum from patients with 6-month long COVID showed increased antibodies against cytomegalovirus, a type of herpesvirus.

This is consistent with evidence suggesting that long COVID symptoms may arise, in part, due to an inflammatory response to the reactivation of a prior herpesvirus infection. The persistence of SARS-CoV-2 in some tissues may also produce an immune response.

These results suggest that binding of the antibodies to proteins from a herpesvirus could contribute to the activation of the complement system. Besides explaining the increased complement activation, these results suggest that antivirals targeting the herpesvirus and SARS-CoV-2 could have the potential to ameliorate long COVID symptoms.

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Long COVID: Study reveals potential cause of prolonged symptoms - Medical News Today

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