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Post-infection functional gastrointestinal disorders following coronavirus disease-19: a prospective follow-up cohort study

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Study design

This prospective cohort study was conducted on adults between July 2022 and February 2023. At the time of the study, China was tough on COVID-19 dominated by Omicron [14, 15], a variant of SARS-CoV-2 and all people were in a population-wide COVID screening in hospital or community with regular universal reverse transcription polymerase chain reaction (RT-PCR) test. All suspicious COVID persons even for asymptomatic infection were referred to local hospitals or large square cabin hospitals for mandatory quarantine. All suspicious infected persons undergoing a diagnostic procedure, such as a nasopharyngeal polymerase chain reaction (PCR) test or chest radiograph to show their lung involvement, had a definite diagnosis of coronavirus infection by their physician. Patients with COVID−19 are included in the study according to inclusion or exclusion criteria as soon as the diagnosis of COVID−19 is confirmed. Gastroenteroscopy including endoscopic biopsy, blood sampling(Blood count, white blood cell count, CPR, PCT, IL−6, IgG and IgM antibody tests for viruses) and other tests (X-rays and ultrasound, Urine routine, stool routine) were needed to exclude other bacterial and viral infections in the whole body or any part of the body or acute gastroenteritis (AG) that could cause GI symptoms. The lag time from diagnosis of COVID−19 to study inclusion is no more than 1 day. All patients received the national protocol of standard treatment without changes.

It consisted of 2 cohorts, a case group that included COVID-19 patients consecutively recruited from Fangcai Hospital, a dedicated COVID care center, in Haikou of Hainan Province, China. Healthy control group included COVID serology negative screeners at our hospital in the same time period. Participants were followed up either outpatient physical or over the telephone at 1, 3, and 6 months using validated Rome III and Rome IV questionnaire and limited objective assessment [1]. The follow-up period from July-August 2022 to February 2023 was more than 6 months. The data from case groups were compared with the 6-month follow-up data on the development of FGID in an age- and sex-matched cohort of healthy subjects. In addition, subjects who met the various diagnostic criteria for FGID in Rome at 6 months of follow-up were advised to come to the clinic for further examination by laboratory and endoscopic methods as well as clinical indications to exclude some diseases such as gastroparesis, SIBO, microscopic colitis, etc. Clinical indicators include duration and frequency of diarrhea, consistency of stool and presence of blood, history of vomiting, fever, cramping abdominal pain and weight loss. The included COVID-19 patients and healthy controls were tested for COVID-19 at 3 and 6 months to exclude COVID-19 reinfection. The questionnaires also included co-morbidities (Hypertension or diabetes), anxiety, irregular diet, sleep quality, and regular exercise sections.

Inclusion criteria of case group were as follows: (1) age between 18 and 85 years old, having a definitive diagnosis of coronavirus with different severity [16, 17] (mild and moderate) using biochemical test data (such as COVID19-SARS-CoV-2 positive, and anti-SARS-CoV-19 IgG and IgM negative) or computed tomography scan of chest and observation of lung involvement;(2) no previous history of clinical confirmation of the diagnosis of any FGID, no GI tumors, reflux esophagitis, ulcerative colitis or other GI diseases, no co-morbidities (Hypertension or diabetes), no history of abdominal surgery, and no any recurrent baseline symptoms of FGID or GI symptoms such as diarrhea, constipation, or abdominal pain; (3) blood sampling, and other tests were needed to exclude AG, bacterial and viral infections;(4) normal findings of gastroscopy and other laboratory tests from the last 6 months of medical examination were required. Healthy control group had no history of COVID-19 or FGID. Biochemical test data (such as COVID19-SARS-CoV-2 negative, and anti-SARS-CoV-19 IgG and IgM negative) are required and the rest of the criteria were the same as for the case group.

The objectives of this study were explained in detail to all participants, and also, partici-pating in this study was fully conscious and based on their desire. Further, written informed consent was obtained from each participant. Meanwhile, Each participant provided a written or electronic informed consent form and the study was approved by the institutional ethics committee of the Second Hospital of Hainan Medical University (reference number: LW2022270).

Definitions

RT-PCR was used to detect SARS-CoV-2 in nasopharyngeal and oropharyngeal samples of subjects [18]. The diagnosis of IBS by the Rome IV diagnostic criteria has changed significantly, the new diagnostic criteria have increased the frequency required to diagnose IBS, and the incidence of IBS has decreased [1]. We used Rome III rather than the most recently described Rome IV criteria as the latter is 50% less sensitive to diagnose IBS [1]. Other types of FGID were diagnosed based on the Rome IV criteria [1].

Dyspepsia refer to postprandial discomfort syndrome, which often manifests itself as postprandial fullness and early satiety (inability to complete a normal meal). Dyspepsia means the same as Functional dyspepsia, and refers only to postprandial discomfort syndrome.

AG was defined as the presence of at least two of the followings: (i) diarrhea, (ii) vomiting, (iii) fever, and (iv) stool culture isolating entero-pathogens [6]. Stool sample of each COVID-19 patient was examined under a microscope for detection of pus cell, RBC or parasites. All suspected stool samples were cultured for Vibrio cholerae, Salmonella, Shigella, Campylobacter and Aeromonas using standard techniques to identify the pathogenic strains.

Patients who showed signs of organ failure (such as persistent oliguria, severe respiratory distress) or required ventilator support or admission to an intensive care unit during treatment for COVID-19 infection were defined as having severe COVID-19. The severity of the COVID-19 [16, 17, 19] was assessed as described: (i) critical (required ventilator), (ii) severe (needed oxygen), (iii) moderate (though pneumonia present, did not require oxygen), and (iv) mild (only upper respiratory symptoms). Those without symptoms at the time of diagnosis of COVID-19 were classified as asymptomatic as categorical variables (yes or no).

Living with frequent (> 5 times/month) infrequent meals and irregular meal times was defined as an irregular diet. The Pittsburgh Sleep Quality Index (PSQI) [20] was used to investigate the sleep quality of patients. The total score of PSQI ranges from 0 to 21, where 7 is the threshold value of sleep quality problem, and the higher score above 7 indicates the poorer sleep quality of the patients, while the opposite indicates the better sleep quality of the patients. Regular exercise is defined by the latest World Health Organization (WHO) Guidelines for Exercise and Sedentary Behavior 2020 [21]. Adults should engage in at least 150–300 min of moderate-intensity aerobic exercise per week, or at least 75–150 min of high-intensity aerobic activity, or an equivalent combination of moderate-intensity and high-intensity exercise; Older adults should have at least 150–300 min of moderate intensity aerobic exercise per week, or at least 75–150 min of high intensity aerobic exercise, or an equivalent combination of moderate and high intensity exercise. The Hamilton Anxiety Scale [22] was used to evaluate the psychological status of the case group, and possible anxiety was considered when the scale score was > 7.

Statistical analysis

Sample size calculation

In this study, the sample size was calculated as 90% power, 99% confidence interval (bilateral) based on previous studies [12, 23, 24] that showed that the mean incidence of FGIDs after acute gastroenteritis is about 21% and a Chinese study that showed the incidence of PI-FGIDs in controls of 8.2% [25]. A total of 155 COVID-19 patients and 155 healthy controls were required in this study, while 194 COVID-19 patients and 194 controls were enrolled since about 10–20% loss could occur at follow-up. Four of 194 COVID-19 patients and 34 of 194 healthy controls were excluded because they had inadequate documentation or were lost during follow-up. Finally, 190 COVID-19 patients and 160 healthy controls were analyzed (Fig. 1).

Fig. 1

Flowchart of this study

Data collection and analysis

SPSS (version 26; SPSS Inc, Chicago, IL) was used for all statistical analyses. Categorical data were presented as proportions, while continuous data were expressed as mean ± standard deviation (SD) or median and range or interquartile range (IQR). Categorical variables were analyzed using χ2 test with Yates correction, where applicable. Parametric and nonparametric continuous data were analyzed using unpaired t-test and Mann-Whitney U test, respectively. Multivariate analysis was performed using stepwise logistic regression. A two-tailed P value < 0.05 was considered significant.

 

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Health Canada approves updated Moderna COVID-19 vaccine

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TORONTO – Health Canada has authorized Moderna’s updated COVID-19 vaccine that protects against currently circulating variants of the virus.

The mRNA vaccine, called Spikevax, has been reformulated to target the KP.2 subvariant of Omicron.

It will replace the previous version of the vaccine that was released a year ago, which targeted the XBB.1.5 subvariant of Omicron.

Health Canada recently asked provinces and territories to get rid of their older COVID-19 vaccines to ensure the most current vaccine will be used during this fall’s respiratory virus season.

Health Canada is also reviewing two other updated COVID-19 vaccines but has not yet authorized them.

They are Pfizer’s Comirnaty, which is also an mRNA vaccine, as well as Novavax’s protein-based vaccine.

This report by The Canadian Press was first published Sept. 17, 2024.

Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

The Canadian Press. All rights reserved.

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These people say they got listeria after drinking recalled plant-based milks

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TORONTO – Sanniah Jabeen holds a sonogram of the unborn baby she lost after contracting listeria last December. Beneath, it says “love at first sight.”

Jabeen says she believes she and her baby were poisoned by a listeria outbreak linked to some plant-based milks and wants answers. An investigation continues into the recall declared July 8 of several Silk and Great Value plant-based beverages.

“I don’t even have the words. I’m still processing that,” Jabeen says of her loss. She was 18 weeks pregnant when she went into preterm labour.

The first infection linked to the recall was traced back to August 2023. One year later on Aug. 12, 2024, the Public Health Agency of Canada said three people had died and 20 were infected.

The number of cases is likely much higher, says Lawrence Goodridge, Canada Research Chair in foodborne pathogen dynamics at the University of Guelph: “For every person known, generally speaking, there’s typically 20 to 25 or maybe 30 people that are unknown.”

The case count has remained unchanged over the last month, but the Public Health Agency of Canada says it won’t declare the outbreak over until early October because of listeria’s 70-day incubation period and the reporting delays that accompany it.

Danone Canada’s head of communications said in an email Wednesday that the company is still investigating the “root cause” of the outbreak, which has been linked to a production line at a Pickering, Ont., packaging facility.

Pregnant people, adults over 60, and those with weakened immune systems are most at risk of becoming sick with severe listeriosis. If the infection spreads to an unborn baby, Health Canada says it can cause miscarriage, stillbirth, premature birth or life-threatening illness in a newborn.

The Canadian Press spoke to 10 people, from the parents of a toddler to an 89-year-old senior, who say they became sick with listeria after drinking from cartons of plant-based milk stamped with the recalled product code. Here’s a look at some of their experiences.

Sanniah Jabeen, 32, Toronto

Jabeen says she regularly drank Silk oat and almond milk in smoothies while pregnant, and began vomiting seven times a day and shivering at night in December 2023. She had “the worst headache of (her) life” when she went to the emergency room on Dec. 15.

“I just wasn’t functioning like a normal human being,” Jabeen says.

Told she was dehydrated, Jabeen was given fluids and a blood test and sent home. Four days later, she returned to hospital.

“They told me that since you’re 18 weeks, there’s nothing you can do to save your baby,” says Jabeen, who moved to Toronto from Pakistan five years ago.

Jabeen later learned she had listeriosis and an autopsy revealed her baby was infected, too.

“It broke my heart to read that report because I was just imagining my baby drinking poisoned amniotic fluid inside of me. The womb is a place where your baby is supposed to be the safest,” Jabeen said.

Jabeen’s case is likely not included in PHAC’s count. Jabeen says she was called by Health Canada and asked what dairy and fresh produce she ate – foods more commonly associated with listeria – but not asked about plant-based beverages.

She’s pregnant again, and is due in several months. At first, she was scared to eat, not knowing what caused the infection during her last pregnancy.

“Ever since I learned about the almond, oat milk situation, I’ve been feeling a bit better knowing that it wasn’t something that I did. It was something else that caused it. It wasn’t my fault,” Jabeen said.

She’s since joined a proposed class action lawsuit launched by LPC Avocates against the manufacturers and sellers of Silk and Great Value plant-based beverages. The lawsuit has not yet been certified by a judge.

Natalie Grant and her seven year-old daughter, Bowmanville, Ont.

Natalie Grant says she was in a hospital waiting room when she saw a television news report about the recall. She wondered if the dark chocolate almond milk her daughter drank daily was contaminated.

She had brought the girl to hospital because she was vomiting every half hour, constantly on the toilet with diarrhea, and had severe pain in her abdomen.

“I’m definitely thinking that this is a pretty solid chance that she’s got listeria at this point because I knew she had all the symptoms,” Grant says of seeing the news report.

Once her daughter could hold fluids, they went home and Grant cross-checked the recalled product code – 7825 – with the one on her carton. They matched.

“I called the emerg and I said I’m pretty confident she’s been exposed,” Grant said. She was told to return to the hospital if her daughter’s symptoms worsened. An hour and a half later, her fever spiked, the vomiting returned, her face flushed and her energy plummeted.

Grant says they were sent to a hospital in Ajax, Ont. and stayed two weeks while her daughter received antibiotics four times a day until she was discharged July 23.

“Knowing that my little one was just so affected and how it affected us as a family alone, there’s a bitterness left behind,” Grant said. She’s also joined the proposed class action.

Thelma Feldman, 89, Toronto

Thelma Feldman says she regularly taught yoga to friends in her condo building before getting sickened by listeria on July 2. Now, she has a walker and her body aches. She has headaches and digestive problems.

“I’m kind of depressed,” she says.

“It’s caused me a lot of physical and emotional pain.”

Much of the early days of her illness are a blur. She knows she boarded an ambulance with profuse diarrhea on July 2 and spent five days at North York General Hospital. Afterwards, she remembers Health Canada officials entering her apartment and removing Silk almond milk from her fridge, and volunteers from a community organization giving her sponge baths.

“At my age, 89, I’m not a kid anymore and healing takes longer,” Feldman says.

“I don’t even feel like being with people. I just sit at home.”

Jasmine Jiles and three-year-old Max, Kahnawake Mohawk Territory, Que.

Jasmine Jiles says her three-year-old son Max came down with flu-like symptoms and cradled his ears in what she interpreted as a sign of pain, like the one pounding in her own head, around early July.

When Jiles heard about the recall soon after, she called Danone Canada, the plant-based milk manufacturer, to find out if their Silk coconut milk was in the contaminated batch. It was, she says.

“My son is very small, he’s very young, so I asked what we do in terms of overall monitoring and she said someone from the company would get in touch within 24 to 48 hours,” Jiles says from a First Nations reserve near Montreal.

“I never got a call back. I never got an email”

At home, her son’s fever broke after three days, but gas pains stuck with him, she says. It took a couple weeks for him to get back to normal.

“In hindsight, I should have taken him (to the hospital) but we just tried to see if we could nurse him at home because wait times are pretty extreme,” Jiles says, “and I don’t have child care at the moment.”

Joseph Desmond, 50, Sydney, N.S.

Joseph Desmond says he suffered a seizure and fell off his sofa on July 9. He went to the emergency room, where they ran an electroencephalogram (EEG) test, and then returned home. Within hours, he had a second seizure and went back to hospital.

His third seizure happened the next morning while walking to the nurse’s station.

In severe cases of listeriosis, bacteria can spread to the central nervous system and cause seizures, according to Health Canada.

“The last two months have really been a nightmare,” says Desmond, who has joined the proposed lawsuit.

When he returned home from the hospital, his daughter took a carton of Silk dark chocolate almond milk out of the fridge and asked if he had heard about the recall. By that point, Desmond says he was on his second two-litre carton after finishing the first in June.

“It was pretty scary. Terrifying. I honestly thought I was going to die.”

Cheryl McCombe, 63, Haliburton, Ont.

The morning after suffering a second episode of vomiting, feverish sweats and diarrhea in the middle of the night in early July, Cheryl McCombe scrolled through the news on her phone and came across the recall.

A few years earlier, McCombe says she started drinking plant-based milks because it seemed like a healthier choice to splash in her morning coffee. On June 30, she bought two cartons of Silk cashew almond milk.

“It was on the (recall) list. I thought, ‘Oh my God, I got listeria,’” McCombe says. She called her doctor’s office and visited an urgent care clinic hoping to get tested and confirm her suspicion, but she says, “I was basically shut down at the door.”

Public Health Ontario does not recommend listeria testing for infected individuals with mild symptoms unless they are at risk of developing severe illness, such as people who are immunocompromised, elderly, pregnant or newborn.

“No wonder they couldn’t connect the dots,” she adds, referencing that it took close to a year for public health officials to find the source of the outbreak.

“I am a woman in my 60s and sometimes these signs are of, you know, when you’re vomiting and things like that, it can be a sign in women of a bigger issue,” McCombe says. She was seeking confirmation that wasn’t the case.

Disappointed, with her stomach still feeling off, she says she decided to boost her gut health with probiotics. After a couple weeks she started to feel like herself.

But since then, McCombe says, “I’m back on Kawartha Dairy cream in my coffee.”

This report by The Canadian Press was first published Sept. 16, 2024.

Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

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B.C. mayors seek ‘immediate action’ from federal government on mental health crisis

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VANCOUVER – Mayors and other leaders from several British Columbia communities say the provincial and federal governments need to take “immediate action” to tackle mental health and public safety issues that have reached crisis levels.

Vancouver Mayor Ken Sim says it’s become “abundantly clear” that mental health and addiction issues and public safety have caused crises that are “gripping” Vancouver, and he and other politicians, First Nations leaders and law enforcement officials are pleading for federal and provincial help.

In a letter to Prime Minister Justin Trudeau and Premier David Eby, mayors say there are “three critical fronts” that require action including “mandatory care” for people with severe mental health and addiction issues.

The letter says senior governments also need to bring in “meaningful bail reform” for repeat offenders, and the federal government must improve policing at Metro Vancouver ports to stop illicit drugs from coming in and stolen vehicles from being exported.

Sim says the “current system” has failed British Columbians, and the number of people dealing with severe mental health and addiction issues due to lack of proper care has “reached a critical point.”

Vancouver Police Chief Adam Palmer says repeat violent offenders are too often released on bail due to a “revolving door of justice,” and a new approach is needed to deal with mentally ill people who “pose a serious and immediate danger to themselves and others.”

This report by The Canadian Press was first published Sept. 16, 2024

The Canadian Press. All rights reserved.

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