Virus World

Regular exercise, good quality sleep, and maintaining a healthy diet may be key to preventing long-term complications following COVID-19 infection. Researchers found women who followed a healthy lifestyle had half of the risk of developing long-COVID compared to those with unhealthy lifestyles.

Women who followed most aspects of a healthy lifestyle, including healthy body weight, not smoking, regular exercise, adequate sleep, high quality diet, and moderate alcohol consumption, had about half the risk of long COVID compared with women without any healthy lifestyle factors, according to a study led by Harvard T.H. Chan School of Public Health.

Source: Harvard

“With ongoing waves of COVID-19, long COVID has created a serious public health burden. Our findings raise the possibility that adopting more healthy behaviors may reduce the risk of developing long COVID,” said Andrea Roberts, senior research scientist in the Department of Environmental Health and senior author of the study. The study appears online February 6, 2023, in JAMA Internal Medicine. It’s estimated that 8-23 million Americans suffer from long COVID, which is defined as having COVID-19 symptoms four weeks or more after initial SARS-CoV-2 infection. Symptoms can include fatigue, fever, and a variety of respiratory, heart, neurological, and digestive symptoms. The researchers analyzed data from more than 32,000 female nurses in the Nurses’ Health Study II, who reported on lifestyle in 2015 and 2017 and reported history of SARS-CoV-2 infection from April 2020 to November 2021. During that time, more than 1,900 participants contracted COVID-19. Among these, 44% developed long COVID. Compared to women without any healthy lifestyle factors, those with five or six had 49% lower risk of long COVID. Among the six lifestyle factors, maintaining a healthy body weight and getting adequate sleep (seven to nine hours daily) were the ones most strongly associated with lower risk of long COVID.

The results also showed that, even among women who developed long COVID, those with a healthier pre-infection lifestyle had 30% lower risk of having symptoms that interfered with their daily life. The authors noted that one possible explanation for the associations they observed is that, based on prior research, an unhealthy lifestyle is associated with increased risk of chronic inflammation and immune dysregulation, which have been linked with increased risk of long COVID. “In the past decades, scientists have accumulated evidence that healthy lifestyle is good for overall health. However, in the U.S. for example, 70% of the population do not have a healthy body weight and 30% do not sleep enough. “Findings from this study suggest that simple lifestyle changes, such as having adequate sleep, may be beneficial for the prevention of long COVID,” said lead author Siwen Wang, research fellow in the Department of Nutrition. Other Harvard Chan School authors included Yanping Li, Yiyang Yue, Changzhen Yuan, Jorge Chavarro, and Shilpa Bhupathiraju.

Funding: Support for the study came from NIH NICHD grant 3R01HD094725-02S1. Other support includes grants U01HL145386, R24ES028521, U01 CA176726, R01 CA67262, and R01 HD057368 from the NIH, the Dean’s Fund for Scientific Advancement Acceleration Award from Harvard Chan School, and Massachusetts Consortium on Pathogen Readiness Evergrande COVID-19 Response Fund Award.

Research published in JAMA Internal Medicine (Feb. 6, 2023):

https://doi.org/10.1001/jamainternmed.2022.6555 

The report distinguished two patterns of liver involvement after COVID-19: acute liver failure that required transplantation and acute hepatitis with injury to the bile system.  On June 7, 2022, the World Health Organization (WHO) and the World Hepatitis Alliance, at their World Hepatitis Summit 2022, released a joint news statement in which they also briefly addressed the current cases of unexplained acute hepatitis (liver inflammation) among young children. There have been some 700 such cases in the last five months, spanning 34 countries, coinciding with the Omicron phase of the pandemic. The United Kingdom and the United States lead in the number of cases, each with more than 200.  The clinical signs of the disease come on suddenly, with a high proportion of children developing liver failure and around six percent needing a liver transplant. Nine have died. The most common symptoms are vomiting and jaundice, the yellowing of the skin and the sclera of the eyes.  Many in the scientific community speculated that the disease fell into the spectrum of the multisystem inflammatory syndrome-children (MIS-C) arising from a previous COVID infection, which can afflict a minority of children and adolescents after the acute phase of COVID has passed and their infections have already cleared, meaning that once acute hepatitis manifests, their COVID tests are negative. Many have also not had antibody tests conducted to confirm previous COVID infections.  Speaking with New Scientist, Dr. Deepti Gurdasani of Queen Mary University of London said, “I think we have seen hepatitis as part of MIS-C before, but not in the numbers that are being seen now.” She explained that the rise could be because Omicron has infected millions of children in a few short months. Many public health officials, including the US Centers for Disease Control and Prevention (CDC) and the WHO, have placed undue emphasis on adenovirus infections, which commonly cause colds and flu-like symptoms in the population. However, they almost never cause liver failure among previously healthy children, or even the immuncocompromised, for that matter. 

Despite experience with adenoviruses and ample expertise on viral infections and liver injury that have been amply documented in the literature, this didn’t stop the CDC from writing on May 6, 2022, “This cluster [in Kentucky], along with recently identified possible cases in Europe, suggest that adenovirus should be considered in the differential diagnosis of acute hepatitis of unknown etiology among children.”  But in their report they clearly stated that on liver biopsies no [adenovirus] viral infections were ever observed. Even with the use of the electron microscope, no viral particles were evident. In the very rare instances where adenoviruses have caused liver failure among immunocompromised children, in 100 percent of cases the adenovirus was detected in liver cells. On May 22 the WHO provided a more nuanced perspective, writing, “While adenovirus is a plausible hypothesis as part of the pathogenesis mechanism [the manner of development of disease], further investigations are ongoing for the causative agent; adenovirus infection (which generally causes mild self-limiting gastrointestinal or respiratory infections in young children) does not fully explain the more severe clinical picture observed with these cases.” Dr. Farid Jalali, a gastroenterologist, has emphatically denounced the claim that these recent unexplained pediatric acute liver failures are associated with the detection of adenovirus in the patients, especially in the context of the COVID-19 pandemic and recent massive waves of Omicron infections.

Adenoviruses are common and can colonize the areas of the respiratory and intestinal tracts. Finding them doesn’t necessarily indicate they were the cause of the disease. He emphasized that public health institutions are doing a disservice to the children and families of the afflicted by suggesting such an association and are only minimizing the dangers posed by the current policies that allow SARS-CoV-2 to persist in human communities.  The debate in the scientific community has been ongoing. However, a recent study from Tel Aviv University has provided new evidence that COVID is indeed responsible for these acute liver failure cases. Lead author Dr. Shiri Cooper and colleagues submitted a report last Friday to the Journal of Pediatric Gastroenterology and Nutrition on five pediatric cases that had recovered from asymptomatic or mild COVID and later suffered acute liver injury. They distinguished two patterns of liver involvement after COVID-19: acute liver failure that required transplantation and acute hepatitis with injury to the bile system. Interestingly, the two patients with liver failure were aged only three and five months, and those older, aged eight to 13, developed a disease pattern similar to their adult counterparts.  In adults, post-COVID liver injury has been described in the medical literature but usually as a late complication of severe COVID and hospitalization that leads to progressive liver failure.  Cooper and colleagues in the current study from Tel Aviv University wrote, “The clinical manifestation of the pediatric patients suggests that the pathogenesis is not related to the severity of acute [COVID] disease” as it is in adults. The disease among children frequently presents several months after the diagnosis of COVID-19. In their study, the mean time from COVID to liver failure was 75 days, which explains why so many of these cases were missed as Long-COVID complications, because children are routinely missed in diagnosing the milder form of acute disease. 

Many of the findings in the children with liver failure have also been seen in adults, such as the swelling and enlargement of the liver. The walls of the gallbladders were thickened, and the bile ducts were dilated. Biopsies of the liver showed extensive inflammation. In other words, the disease process that has been attributed to adults after their COVID infection has distinct parallels with these children and their acute liver inflammation. Because of the claimed association with adenovirus, the authors of the Israeli study also attempted to investigate this hypothesis.  First, they commented on published results by the European CDC on 14 cases. None showed adenovirus in any residual liver cells, called hepatocytes: “One case underwent adenovirus PCR of liver tissue which was negative.” In another case series of six patients, none of the liver biopsies showed the presence of any adenovirus particles. But as already noted, in rare cases of adenovirus-induced liver failure, liver biopsies in all the cases showed viral particles were present.  In the five patients in Israel, “The adenovirus stain was negative in all, and the histologic features [under the microscope] were not suggestive of adenovirus hepatitis. Three patients had adenovirus PCR performed from whole blood, and in one, it was positive. However, as the liver histology was not suggestive of adenovirus infection, we did not consider it as the culprit for the hepatitis.” As to the mechanism of injury, the authors suggested that damage to the immune system from COVID is likely the cause, and considerable effort is needed to understand these complex processes. It is all the more necessary that public health authorities stop being obstructionists, heed the weight of the evidence that has already been presented, and acknowledge the dangers posed by COVID and the reckless “herd immunity” policy that exposes children to unnecessary harm.  Dr. Lisa Iannattone stated bluntly on Twitter, “Anyone putting forth the hypothesis that there are two novel pediatric liver failure outbreaks caused by two different viruses happening at the same time is not someone to be taken seriously. I don’t care what ‘very serious institution’ they work for. This is absurd. It’s COVID.”

Research Cited available in the Journal of Pediatric Gastroenterology and Nutrition (June 10, 2022):

https://journals.lww.com/jpgn/abstract/9900/long_covid_19_liver_manifestation_in_children.84.aspx 

COVID-19 is associated with higher risks of cardiovascular disease and death in the short- and long-term, according to a study in nearly 160,000 participants published today in Cardiovascular Research, a journal of the European Society of Cardiology (ESC). Compared to uninfected individuals, the likelihood of COVID-19 patients dying was up to 81 times higher in the first three weeks of infection and remained five times higher up to 18 months later. "COVID-19 patients were more likely to develop numerous cardiovascular conditions compared to uninfected participants, which may have contributed to their higher risks of death," said study author Professor Ian C.K. Wong of the University of Hong Kong, China. "The findings indicate that patients with COVID-19 should be monitored for at least a year after recovering from the acute illness to diagnose cardiovascular complications of the infection, which form part of long COVID." This study compared the occurrence of cardiovascular conditions and death in infected versus uninfected individuals recruited before December 2020, when no vaccines were available in the UK. More than 7,500 patients with COVID-19 infection diagnosed from March 16, 2020 to November 30, 2020 were identified from UK Biobank. Each patient was matched with up to 10 individuals without COVID-19 during the study period (March 16, 2020 to the end of follow-up on August 31, 2021) and a historical cohort before the pandemic (March 16, 2018 to November 30, 2018).

Each uninfected group had more than 70,000 participants who were similar to the COVID-19 group for age, sex, smoking, diabetes, high blood pressure, cardiovascular and other health conditions, body mass index, ethnicity, and deprivation. In all three groups, the average age was 66 years and there were nearly equal numbers of women and men. Professor Wong explained, "The historical control cohort was included to rule out the effect of routine healthcare services being reduced or canceled during the pandemic, which led to worsening health and increased mortality even in uninfected people." Data were obtained from medical and death records for outcomes including major cardiovascular disease (a composite of heart failure, stroke and coronary heart disease); numerous cardiovascular conditions such as stroke, atrial fibrillation and myocardial infarction; death from cardiovascular disease; and all-cause death. Associations were evaluated for the acute phase (within 21 days of COVID-19 diagnosis) and the post-acute phase (starting at 22 days after diagnosis and continuing up to 18 months). Participants with a history of a particular outcome were excluded from that analysis. Compared with the two uninfected cohorts, patients with COVID-19 were approximately four times more likely to develop major cardiovascular disease in the acute phase and 40% more likely in the post-acute phase. Compared to uninfected individuals, the risk of death in COVID-19 patients was up to 81-fold higher in the acute phase and five-fold higher in the post-acute phase. Patients with severe COVID-19 were more likely to develop major cardiovascular disease or die than non-severe cases.

COVID-19 patients had a greater likelihood of several cardiovascular conditions compared with uninfected participants in both the short- and long-term including myocardial infarction, coronary heart disease, heart failure, and deep vein thrombosis. Risks of some cardiovascular conditions—for example stroke and atrial fibrillation—were elevated in COVID-19 patients in the short-term but then returned to normal levels. Professor Wong said, "This study was conducted during the first wave of the pandemic, and future research should evaluate subsequent outbreaks. Previous research has indicated that COVID-19 vaccination may prevent complications, and further studies are needed to investigate its effectiveness in reducing the risks of cardiovascular disease and death after COVID-19 infection in patients with COVID-19 vaccination compared to those without vaccination." ESC spokesperson Professor Héctor Bueno of the National Centre for Cardiovascular Research (CNIC), Madrid, Spain said, "COVID-19 has had a huge impact on patients with cardiovascular disease, who were less likely to receive optimal care during the pandemic and more likely to die from the infection. This study shows that COVID-19 also increases the risk of having cardiovascular complications and dying in the first weeks after the infection and remains high for months, suggesting that specific cardiovascular monitoring may be appropriate in these patients."

Cited study published in Cardiovascular Research (Jan. 19, 2023):

https://doi.org/10.1093/cvr/cvac195

The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—also referred to as Long COVID—have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear. In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, including contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls. At 6 months after infection, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.59, 1.93) and incident post-acute sequelae (HR = 1.50, 95% CI: 1.46, 1.54), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders.

The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI. A new analysis using the US Department of Veterans Affairs national healthcare databases demonstrates that Long COVID can occur after breakthrough SARS-CoV-2 infection; however, the risk of death attributable to COVID and incidence of post-acute sequelae were substantially reduced (but not fully eliminated) compared to unvaccinated individuals.

Published in Nature Medicine (May 25, 2022):

https://www.nature.com/articles/s41591-022-01840-0 

The study adds to growing evidence that vaccination helps protect against Covid in a number of ways. Being fully vaccinated against Covid-19 not only cuts the risk of catching it, but also of an infection turning into long Covid, research led by King's College London suggests. It shows that in the minority of people who get Covid despite two jabs, the odds of developing symptoms lasting longer than four weeks are cut by 50%. This is compared with people who are not vaccinated. So far, 78.9% of over-16s in the UK have had two doses of a Covid vaccine. Many people who get Covid recover within four weeks but some have symptoms that continue or develop for weeks and months after the initial infection - sometimes known as long Covid. It can happen after people experience even mild coronavirus symptoms. The researchers, whose work was published in The Lancet Infectious Diseases, say it is clear that vaccinations are saving lives and preventing serious illness, but the impact of vaccines on developing long-lasting illness has been less certain.  They analysed data gathered from the UK Zoe Covid Study app, which tracks people's self-reported symptoms and vaccines and tests.