Who’ll Get Long COVID? Just a Look at a Patient Gives Clues

Authors: Dennis Thompson Jul 19, 2022 The Indiana Gazette

ometimes just looking at a person can give clues to their likelihood of developing long COVID after a bout with the virus.

For example, obese people are five times more likely to suffer long COVID symptoms that persist at least three months after their infection clears, a major new U.S. study finds.

Another risk factor: Experiencing hair loss during COVID-19 illness, the same study found.

Headache and sore throat during infection also greatly increase a person’s risk of long-haul symptoms, the researchers added.

However, the results also showed that other risk factors for COVID-19 infection do not necessarily mean a person will develop long COVID, noted senior researcher Eileen Crimmins, chair of gerontology for the University of Southern California and director of the USC/UCLA Center on Biodemography and Population Health.

“What’s somewhat more interesting are the things that didn’t matter,” Crimmins said. “Gender didn’t predict long COVID. Race/ethnicity didn’t predict long COVID. And having conditions like hypertension [high blood pressure], heart disease, cancer, they didn’t predict long COVID.”

Overall, 23% of people infected with COVID-19 can be expected to develop long-haul symptoms, regardless of whether their infection was severe enough to require hospitalization, Crimmins and her colleagues reported. The study was published online recently in the journal Scientific Reports.

The World Health Organization defines long COVID as symptoms that last 12 weeks or longer after the initial infection has cleared, the researchers said.

“A significant number of people may have trouble working, taking care of their families, doing the things they need to do day-to-day because they’ve had the condition,” Crimmins said. “So, it’s not a nothing disease.”

These numbers are based on the Understanding America Study COVID-19 National Panel, an ongoing regular survey of more than 8,400 U.S. adults.

Starting every two weeks in March 2020, panel members were asked to fill out a questionnaire detailing their health status and any symptoms they might be having.

During the following year, about 10% of total participants reported that they’d been diagnosed with or tested positive for COVID-19.

The researchers focused in on 308 people who had COVID-19 and had reported their health status and symptoms before, during, and at least three months after their initial diagnosis.

What factors influenced the odds of long COVID the most? Obesity increased a person’s risk of long COVID by nearly five and a half times, the results showed. Other prominent risk factors included hair loss during infection, which increased sevenfold the risk of long COVID. Headache and sore throat each increased a person’s risk by more than three times.

It’s likely that obesity and hair loss are both tied to the amount of inflammation a person suffers during their COVID-19 infection, which can wreak havoc on their body’s organs, explained Dr. William Schaffner, medical director of the National Foundation for Infectious Diseases.

“Perhaps obesity allows that inflammation to persist for a longer period of time, therefore resulting in symptoms,” Schaffner said. “Hair loss is kind of new to me, but that’s obviously going to be some sort of symptom that relates somehow to inflammation.”

Surprisingly, age, gender, race, education, smoking, and preexisting health conditions like diabetes or asthma didn’t appear to influence the risk of long COVID.

The most common symptoms people developed during COVID that persisted months later included:

  • Headache (22%)
  • Runny or stuffy nose (19%)
  • Abdominal discomfort (18%)
  • Fatigue (17%)
  • Diarrhea (13%)

The study did not find other symptoms that have been commonly reported by long COVID-19 patients, including brain fog and joint pain, Schaffner noted.

“So there are some things that reinforce what’s in the literature and some other things that are a little different,” Schaffner said.

Despite that, Schaffner praised the study as a “noteworthy addition to the literature” that should help the many long COVID centers that have opened up around the country to deal with this phenomenon.

“The main thing I take away from this is that long COVID is not unusual. In fact, it’s rather common,” Schaffner said. “It’s persistent and it will require a great deal of medical attention going forward. A lot of medical resources will have to be devoted to this, and those resources will largely be outside the hospital, including supportive care, physical therapy and even some psychological support for these patients.”

Crimmins added it could take years, and even decades, to fully understand the long-term effects of COVID-19.

Research into the 1918 influenza pandemic found that fetuses in utero when moms caught the flu had a 25% higher risk of heart disease by the time they were in their 70s, Crimmins noted.

“There are things that may happen in this population to their underlying health that may not be immediately obvious, but could have relatively significant long-term effects,” Crimmins said of long COVID patients.

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Scientists propose cause of symptoms, treatment for long COVID-19

Authors: Gary Van Beusekom | News Writer | CIDRAP News   Posted June 10, 2022

Two studies to be presented at upcoming professional society meetings suggest that some long COVID-19 symptoms may be related to the effect of SARS-CoV-2 on the vagus nerve and that the use of enhanced external counterpulsation (EECP)—which increases blood flow—can improve some of those symptoms, respectively.

Long COVID may affect up to 15% of those who survive their infections, causing symptoms such as fatigue, muscle pain, and cognitive problems that linger for months. Neither study has been peer-reviewed, and the second one comes with the added caveat that it was conducted by an EECP provider.

Long COVID, vagus nerve symptoms may overlap

At the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), slated for Apr 23 to 26 in Lisbon, Portugal, a team led by researchers in Spain will discuss the role of the vagus nerve in long COVID, according to an ECCMID news release.

The vagus nerve runs from the brain into the torso, heart, lungs, intestines, and several muscles, including those involved in swallowing. It has a role in heart rate, speech, the gag reflex, the transfer of food from the mouth to stomach, transporting food through the intestines, perspiration, and other bodily functions.

The study authors said that SARS-CoV-2 infection may lead to long COVID symptoms such as dysphonia (voice problems), dysphagia (difficulty swallowing), dizziness, tachycardia (rapid heart rate), orthostatic hypotension (low blood pressure), and diarrhea. Long COVID has been reported to last for months to more than a year.

In the observational study, the researchers evaluated the morphologic and functional aspects of the vagus nerve in 348 patients diagnosed as having long COVID at a Spanish hospital from March to June 2021. Of the 348, 228 (66%) had at least one symptom that could be attributed to vagus nerve dysfunction (VND).

The ongoing study involved the first 22 participants identified as having at least one VND symptom; 91% of them were women, and the median age was 44 years. The most common VND symptoms were diarrhea (73%), tachycardia (59%), dizziness, dysphagia and dysphonia (45% each), and orthostatic hypotension (14%).

Nineteen of 22 participants (86%) had three or more VND symptoms with a median duration of 14 months. Ultrasound examination revealed that at 6 (27%) had alterations of the vagus nerve in the neck, including thickening of the nerve and increased echogenicity, which indicates mild inflammatory changes.

Thoracic ultrasound showed flattened diaphragmatic curves, indicating abnormal breathing, in 10 participants (46%). Ten of 16 patients (63%) had lower maximum inspiration pressures, indicating weakness of the muscles involved in breathing.

Thirteen of 18 patients (72%) had impaired eating and digestive function, including self-reported dysphagia. Among 19 patients assessed for gastric and bowel function, 8 (42%) had impaired ability to move food from the esophagus to the stomach, with 2 of these 8 reporting difficulty swallowing.

Nine of 19 patients (47%) had gastroesophageal acid reflux, with 4 of these 9 again having problems moving food to the stomach and 3 with hiatal hernia (bulging of the upper stomach through the diaphragm into the chest cavity).

A Voice Handicap Index 30 test (a standard method of measuring voice function) produced abnormal results in 8 of 17 patients (47%), indicating that 7 of the 8 had dysphonia.

“Our findings so far thus point at vagus nerve dysfunction as a central pathophysiological feature of long COVID,” the researchers said in the release.

Improvement in functional scores, fatigue after EECP

In a retrospective study to be presented this week at the American College of Cardiology’s (ACC’s) virtual Cardiovascular Summit, scientists from EECP provider Flow Therapy evaluated the effect of the therapy in 50 COVID-19 survivors, according to an ACC news release. Twenty patients had coronary artery disease (CAD), while 30 did not; average age was 54 years.

EECP uses contracting and relaxing pneumatic cuffs on the calves, thighs, and lower hip area to provide oxygen-rich blood to the heart muscle, brain, and the rest of the body. Each session takes 1 hour, and patients may undergo as many as 35 sessions over 7 weeks.

All patients completed the Seattle Angina Questionnaire-7 (SAQ7), Duke Activity Status Index (DASI), PROMIS Fatigue Instrument, Rose Dyspnea Scale (RDS), and the 6-minute walk test (6MWT) before and after they completed 15 to 35 hours of EECP therapy.

The analysis showed statistically significant improvements in all areas assessed, including 25 more points for health status on the SAQ7 (range, 0 to 100), 20 more points for functional capacity on DASI (range, 0 to 58.2), 6 fewer points for fatigue on PROMIS (range, 4 to 20), 50% lower shortness of breath score on the RDS, and 178 more feet on the 6MWT.

The change from baseline among participants who had long COVID but not CAD was significant for all end points, but there was no difference between long COVID patients with or without CAD.

“Emerging data shows that long COVID is a disease that impacts the health of vessels, also known as endothelial function,” senior author Sachin Shah, PharmD, said in the release. “EECP is a disease-modifying, non-invasive therapy that has previously shown to improve endothelial function in controlled clinical trials.”

Shah said that several study participants weren’t able to work at the beginning of the study. “Remarkably, all patients at this point were able to successfully return back to work after undergoing treatment,” he said. “These patients also showed improvement in ‘brain fog,’ which is a common symptom of long COVID.”

The researchers called for larger studies with a control group receiving sham therapy to validate their findings.

Covid-19: UK studies find gastrointestinal symptoms are common in children

Authors: Susan Mayor BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3484 (Published 07 September 2020)Cite this as: BMJ 2020;370:m3484

Gastrointestinal symptoms are common in children infected with SARS-CoV-2 and should trigger tests for the virus, researchers have said.

A prospective study of 992 healthy children (median age 10.1 years) of healthcare workers from across the UK found that 68 (6.9%) tested positive for SARS-CoV-2 antibodies.1 Half of the children testing positive reported no symptoms, but for those that did the commonest were fever (21 of 68, 31%); gastrointestinal symptoms, including diarrhoea, vomiting, and abdominal cramps (13 of 68, 19%); and headache (12 of 68, 18%).

Latest findings from the Covid-19 Symptom Study app,2 which was launched in late March to track people’s symptoms, also show that gastrointestinal symptoms occur frequently in children with positive swab tests.3

Tom Waterfield, lead author of the antibodies study, told The BMJ, “Based on our findings I think that gastrointestinal symptoms should be added to the current list—high temperature, cough, and loss or change in sense of smell or taste—that trigger testing for coronavirus.” He added, “Diarrhoea and vomiting in children should trigger a test.”

Modelling showed that gastrointestinal symptoms were significantly associated with the presence of SARS-CoV-2 antibodies, in addition to known household contact with confirmed SARS-CoV-2, fatigue, and changes in sense of smell or taste.

“Although diarrhoea and vomiting may not be on the official covid-19 testing strategy, we need to be cautious in children with these symptoms,” said Waterfield, senior lecturer at Queen’s University Belfast and paediatric emergency medicine physician at the Royal Belfast Hospital for Sick Children. “They need to have had 48 hours clear of gastrointestinal symptoms before they go back to school to help reduce the potential spread of the virus.”

Tim Spector, the study lead and professor of genetic epidemiology at King’s College London, said, “Looking at data from 250 000 children we found those with a positive swab test have a different range of symptoms to adults. Cough and shortness of breath are much less frequent and gastrointestinal problems, especially loss of appetite, more frequent. Fever is still a feature, as in adults.”

He said that the study confirmed the need to add a wider range of symptoms to those listed for covid-19. “Around 50% of children did not have the three core adult symptoms (high temperature, cough, and loss or change in sense of smell or taste) and may present with a wide range of non-specific symptoms, such as malaise and loss of appetite, although skin rash affected one in six,” he said. “The key is for parents to keep children at home with these non-specific signs until they feel better, until tests get more rapid and accessible.”

Spector is asking parents to start logging information for their children on the app, which invites users to report regularly on their health. He added that the team is adding school specific features to help provide data on infection rates related to schools.

References

  1. Waterfield T, Watson C, Moore R, et al. Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study. medRxiv 2020.08.31.20183095 [Preprint]. 2 September 2020. www.medrxiv.org/content/10.1101/2020.08.31.20183095v1.
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    . Covid-19: Researchers launch app to track spread of symptoms in the UK. BMJ2020;368:m1263. doi:10.1136/bmj.m1263 pmid:32220898FREE Full Text

Link between fever, diarrhea, severe COVID-19, and persistent anti-SARS-CoV-2 antibodies

Authors: By Dr. Liji Thomas, MD Jan 7 2021

Ever since the coronavirus disease 2019 (COVID-19) pandemic began, there have been many attempts to understand the nature and duration of immunity against the causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

A new preprint research paper appearing on the medRxiv* server describes a link between the persistence of neutralizing antibodies against the virus, disease severity, and specific COVID-19 symptoms.

Permanent immunity is essential if the pandemic is to end. In the earlier SARS epidemic, antibodies were found to last for three or more years after infection in most patients. With the current virus, it may last for six or more months at least, as appears from some reports. Other researchers have concluded that immunity wanes rapidly over the same period, with some patients who were tested positive for antibodies becoming seronegative later on. This discrepancy may be traceable to variation in testing methods, sample sizes and testing time points, as well as disease severity.

Study details

The current study looked at a population of over a hundred convalescent COVID-19 patients, testing most of them for antibodies at five weeks and three months from symptom resolution.

The researchers used a multiplex assay that measured the Immunoglobulin G (IgG) levels against four SARS-CoV-2 antigens, one from SARS-CoV, and four from circulating seasonal coronaviruses. In addition, they carried out an inhibition assay against SARS-CoV-2 spike receptor-binding domain (RBD)-angiotensin-converting enzyme 2 (ACE2) binding and a neutralization assay against the virus. The antibody titers were then plotted against various clinical features and demographic factors.

Antibody titers higher in COVID-19 convalescents

The researchers found that severe disease is correlated with advanced age and the male sex. Patients with underlying vascular disease were more likely to be hospitalized with COVID-19, but those with asthma were relatively spared.

Convalescent COVID-19 patients had higher IgG levels against all four SARS-CoV-2 antigens, relative to controls, and in 98% of cases, at least one of the tests was likely to show higher binding compared to controls. IgGs targeting the viral spike and RBD were likely to be much more discriminatory between SARS-CoV-2 patients and controls. Interestingly, anti-SARS-CoV IgG, as well as anti-seasonal betacoronavirus antibodies, were likely to be higher in these patients.

Anti-spike and anti-nucleocapsid IgG levels, as well as neutralizing antibody titers, were higher in convalescent hospitalized COVID-19 patients than in convalescent non-hospitalized patients, and the titers were positively associated with disease severity.Antibodies against SARS-CoV-2 persist three months after COVID-19 symptom resolution. Sera from COVID-19 convalescent subjects (n=79) collected 5 weeks (w) and 3 months (m) after symptom resolution were subjected to multiplex assay to detect IgG that binds to SARS-CoV-2 S, NTD, RBD and N antigens (A), to RBD-ACE2 binding inhibition assay (B), and to SARS-CoV-2 neutralization assay (C). Dots, lines, and asterisks in red represent non-hospitalized (n=67) and in blue represent hospitalized (n=12) subjects with lines connecting the two time points for individual subjects (*p<0.05 and **p<0.01 by paired t test).Antibodies against SARS-CoV-2 persist three months after COVID-19 symptom resolution. Sera from COVID-19 convalescent subjects (n=79) collected 5 weeks (w) and 3 months (m) after symptom resolution were subjected to multiplex assay to detect IgG that binds to SARS-CoV-2 S, NTD, RBD and N antigens (A), to RBD-ACE2 binding inhibition assay (B), and to SARS-CoV-2 neutralization assay (C). Dots, lines, and asterisks in red represent non-hospitalized (n=67) and in blue represent hospitalized (n=12) subjects with lines connecting the two time points for individual subjects (*p<0.05 and **p<0.01 by paired t test).

Clinical correlates of higher antibody titer

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When antibody titers in non-hospitalized subjects were compared with clinical and demographic variables, they found that older males with a higher body mass index (BMI) and a Charlson Comorbidity Index score >2 were likely to have higher antibody titers. COVID-19 symptoms that correlated with higher antibody levels in these patients comprise fever, diarrhea, abdominal pain and loss of appetite. Chest tightening, headache and sore throat were associated with less severe symptoms.

The link between the specific symptoms listed above with higher antibody titers could indicate that they mark a robust systemic inflammatory response, which in turn is necessary for a strong antibody response. Diarrhea may mark severe disease, but it is strange that in this case, it was not more frequent in the hospitalized cohort. Alternatively, diarrhea may have strengthened the immune antibody response via the exposure of the virus to more immune cells via the damaged enteric mucosa. More study is required to clarify this finding.

Potential substitute for neutralizing assay

The binding assay showed that the convalescent serum at five weeks inhibited RBD-ACE2 binding much more powerfully than control serum. Neutralizing activity was also higher in these sera, but in 15% of cases, convalescent patients showed comparable neutralizing antibody titers to those in control sera. On the whole, however, there was a positive association between neutralizing antibody titer, anti-SARS-CoV-2 IgG titers, and inhibition of ACE2 binding.

Persistent immunity at three months

This study also shows that SARS-CoV-2 antibodies persist in these patients at even three months after symptoms subside, with persistent IgG titers against the SARS-CoV-2 spike, RBD, nucleocapsid and N-terminal domain antigens. Binding and neutralization assays remained highly inhibitory throughout this period. The same was true of antibodies against the other coronaviruses tested as well, an effect that has been seen with other viruses and could be the result of cross-reactive anti-SARS-CoV-2 antibodies. Alternatively, it could be due to the activation of memory B cells formed in response to infection by the seasonal beta-coronaviruses.

Conclusion

IgG titers, particularly against S and RBD, and RBD-ACE2 binding inhibition better differentiate between COVID-19 convalescent and naive individuals than the neutralizing assay,” the researchers concluded.

These could be combined into a single diagnostic test, they suggest, with extreme sensitivity and specificity. The correlation with neutralizing antibody titers could indicate that the neutralizing assay, which is more expensive, sophisticated and expensive, as well as more dangerous for the investigators, could be replaced by the other antibody tests without loss of value.

In short, the study shows that specific antibodies persist for three months at least following recovery; antibody titers correlate with COVID-19-related fever, loss of appetite, abdominal pain and diarrhea; and are also higher in older males with more severe disease, a higher BMI and CCI above 2. Further research would help understand the lowest protective titer that prevents reinfection, and the duration of immunity.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.Journal reference:

COVID-19-associated diarrhea

World J Gastroenterol. 2021 Jun 21; 27(23): 3208–3222.Published online 2021 Jun 21. doi: 10.3748/wjg.v27.i23.3208PMCID: PMC8218355PMID: 34163106

Authors: Klara MegyeriÁron DernovicsZaid I I Al-Luhaibi, and András Rosztóczy

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged as a highly virulent respiratory pathogen that is known as the causative agent of coronavirus disease 2019 (COVID-19). Diarrhea is a common early symptom in a significant proportion of patients with SARS-CoV-2 infection. SARS-CoV-2 can infect and replicate in esophageal cells and enterocytes, leading to direct damage to the intestinal epithelium. The infection decreases the level of angiotensin-converting enzyme 2 receptors, thereby altering the composition of the gut microbiota. SARS-CoV-2 elicits a cytokine storm, which contributes to gastrointestinal inflammation. The direct cytopathic effects of SARS-CoV-2, gut dysbiosis, and aberrant immune response result in increased intestinal permeability, which may exacerbate existing symptoms and worsen the prognosis. By exploring the elements of pathogenesis, several therapeutic options have emerged for the treatment of COVID-19 patients, such as biologics and biotherapeutic agents. However, the presence of SARS-CoV-2 in the feces may facilitate the spread of COVID-19 through fecal-oral transmission and contaminate the environment. Thus gastrointestinal SARS-CoV-2 infection has important epidemiological significance. The development of new therapeutic and preventive options is necessary to treat and restrict the spread of this severe and widespread infection more effectively. Therefore, we summarize the key elements involved in the pathogenesis and the epidemiology of COVID-19-associated diarrhea.

For More Information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218355/