Study Finds Teenage Boys Six Times More Likely To Suffer Heart Problems From Vaccine Than Be Hospitalized by COVID

Authors; Paul Joseph Watson via Summit News,

Research conducted by the University of California has found that teenage boys are six times more likely to suffer from heart problems caused by the COVID-19 vaccine than to be hospitalized as a result of COVID-19 itself.

“A team led by Dr Tracy Hoeg at the University of California investigated the rate of cardiac myocarditis – heart inflammation – and chest pain in children aged 12-17 following their second dose of the vaccine,” reports the Telegraph.

“They then compared this with the likelihood of children needing hospital treatment owing to Covid-19, at times of low, moderate and high rates of hospitalisation.”

Researchers found that the risk of heart complications for boys aged 12-15 following the vaccine was 162.2 per million, which was the highest out of all the groups they looked at.

This compares to the risk of a healthy boy being hospitalized as a result of a COVID infection, which is around 26.7 per million, meaning the risk they face from the vaccine is 6.1 times higher.

Even during high risk rates of COVID, such as in January this year, the threat posed by the vaccine is 4.3 times higher, while during low risk rates, the risk of teenage boys suffering a “cardiac adverse event” from the vaccine is a whopping 22.8 times higher.

The research data was based on a study of adverse reactions suffered by teens between January and June this year.

In a sane world, such data should represent the nail in the coffin for the argument that teenagers and children should be mandated to take the coronavirus vaccine, but it obviously won’t.

In the UK, the government is pushing to vaccinate 12-15-year-olds, even without parental consent, despite the Joint Committee on Vaccination and Immunisation (JCVI) advising against it.

Meanwhile, in America, Los Angeles County school officials voted unanimously to mandate COVID shots for all

Long COVID’s daunting toll seen in study of pandemic’s earliest patients

Authors: Melissa Healy   6 hrs ago

COVID-19 patients in Wuhan were among the pandemic’s first victims, and a comprehensive new study finds that a year after shaking the coronavirus, survivors were more likely than their uninfected peers to suffer from mobility problems, pain or discomfort, anxiety and depression.

detailed accounting of 1,276 people hospitalized for COVID-19 in the pandemic’s opening months reveals that a full year later, almost half continued to report at least one lingering health problem that is now considered a symptom of “long COVID.”

One out of five said they had continued fatigue and/or muscle weakness, and 17% said they were still experiencing sleep difficulties. Just over one in four said they were suffering anxiety or depression in the wake of their bout with the SARS-CoV-2 virus.

For the growing number of patients who identify themselves as COVID “long haulers,” the new accounting offers cause for optimism — and concern. The period from six to 12 months after infection brought improvement for many. But most patients struggling with symptoms at the six-month mark were not yet well six months later.

The findings, catalogued by a team of Chinese researchers, were published late Thursday in the medical journal Lancet.

“This is not good news,” said David Putrino, a rehabilitation specialist who works with COVID long haulers at Mount Sinai Hospital in New York. “If you run the numbers here, about one-third of the group that had persistent symptoms are getting better after 12 months, while two-thirds are not.”

Putrino also called the findings a “wake-up call” to public health officials that even when the pandemic is over — a distant enough prospect in the midst of a fourth wave of infections — its downstream consequences will not be.

“We’re going to need resources for many years to come to deal with these patients,” he said.

There will be a lot of them. More than 87,000 COVID-19 patients are being hospitalized each day in the United States, and 2.7 million have receiving hospital care in the past year alone.

The half who contend with persistent symptoms will show up in doctors’ offices with clusters of vague and perplexing complaints including brain fog, heart palpitations, pain and exhaustion. And despite emerging evidence that time and specialized treatment can help many to improve, few will have the wherewithal to spend months in intensive rehabilitation for their symptoms, Putrino said.

An editorial published alongside the new study noted that only 0.4% of COVID long haulers are receiving rehabilitative treatment for their symptoms.

Even as scientists puzzle over the common biological mechanisms of long COVID’s diverse symptoms, healthcare providers “must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualised, patient-oriented goals, with an appropriately trained workforce,” Lancet’s editors wrote.

The new research also offered some glimmers of hope.

When the study’s COVID-19 patients were examined at six months, 68% said they had at least one of 15 symptoms considered hallmarks of long COVID, which is also known as Post-Acute Sequelae of COVID, or PASC. At one year, 49% were still afflicted by at least one of those symptoms.

The proportion of patients with ongoing muscle weakness and fatigue dropped from 52% to 20% during that time. Patients experiencing loss of smell dropped from 11% to 4%, and those afflicted with sleep problems fell from 27% to 17%. The 22% who reported hair loss at six months dwindled to 11% a full year out.

At the same time, the numbers of patients reporting breathing difficulties saw a slight increase, rising from 26% at six months to 30% after a year. Likewise, patients who reported new depression or anxiety increased from 23% to 26% during that period.

Study co-author Xiaoying Gu from the China-Japan Friendship Hospital in Beijing said the slight uptick in anxiety and depression was, like all of long COVID’s symptoms, hard to explain.

The psychiatric symptoms “could be caused by a biological process linked to the virus infection itself, or the body’s immune response to it,” he said. “Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health or loss of employment associated with illness.”

Patients who required mechanical ventilation were more likely than those with less severe illness to have measurable lung impairment and abnormal chest X-rays at both six and 12 months.

But in the tally of more subjective long COVID symptoms, the difference between the most severely ill and those who required no supplemental oxygen at all was very small.

That finding underscores the fact that even patients who are only mildly ill are at risk of developing a range of persistent symptoms.

Of the study population’s 479 patients who held jobs when the pandemic struck, 88% had returned to work a year after their illness. Most of the 57 who did not return said they either could not or were unwilling to do the tasks required of them.

The findings from the Wuhan patients also tracked with the widespread observation that persistent post-COVID infection symptoms are more common in women than in men. Women who had been hospitalized for COVID-19 were twice as likely as their male counterparts to report depression or anxiety 12 months later. In addition, they were close to three times as likely to show evidence of impaired lung function, and 43% more likely to report symptoms of fatigue and muscle weakness.

All of the study’s participants were treated at a single hospital in Wuhan, where reports of a mysterious new form of pneumonia first surfaced in December 2019. The researchers followed a large group of patients sickened in the first five months that the outbreak.

That makes the Lancet report one of the earliest and largest accounts of lingering COVID-19 symptoms to be tallied and vetted by other researchers, and the only one to compare such patients to a group of uninfected peers matched on a wide range of demographic and health attributes.

One thing is already clear, the journal editors noted: “Long COVID is a modern medical challenge of the first order.”

This story originally appeared in Los Angeles Times.

Nearly 3 in 5 people worldwide have suffered sleep problems during COVID pandemic

Authors: by Study Finds South West News Service writer William Janes contributed to this report

TEMPE, Ariz. — Find yourself struggling to fall asleep and stay asleep more often during the pandemic? You’re far from alone. In fact, sleeping issues are burdening people around the world, with more than nearly six out of 10 people across the globe suffering from poor sleep during COVID, new research shows.

The study involving people from 79 countries around the globe reveals that 56.5 percent of people have experienced some kind of sleep disturbance in the pandemic. Almost two-thirds of those polled dealt with a “delayed sleep” pattern, which was associated with little change in sleep duration or time spent in bed, but a later bedtime and increased nightmares and naps.

The second most common sleep pattern change, experienced by one in five people, was the “sleep lost and fragmented” pattern. Scientists say these people went to bed later and had a shorter time in bed attempting to sleep – in essence, their sleep was restricted, lower in quality, and they were less likely to compensate for it with naps. Women are more likely to experience this disruption than men, results show.

Around one in 10 tended to be “sleep opportunists,” meaning they had significantly restricted sleep opportunities before the pandemic, but spent a lot more time in bed and had the longest sleep duration compared to any of the others. Despite the better sleep, those people also reported the greatest change in their daily routines, which was associated with a lower likelihood of being employed and greater family stress.

The least common sleep pattern was “dysregulated and distressed.” This was experienced by 5 percent of people surveyed. These individuals had the worst sleep deterioration along with more nightmares and naps, and had the worst insomnia symptoms.

“Overall, sleep disturbances were heightened, with 56.5 per cent of our sample reporting clinical levels of insomnia symptoms during the pandemic,” says Dr. Megan Petrov, an assistant professor in the College of Nursing and Health Innovation at Arizona State University, in a statement. “Sleep is an essential part of living, just like air, water and food. Your health and functioning are compromised when the quality of the air you breathe, the water you drink and the food you eat are poor. This is also the case if your sleep is poor quality and insufficient in quantity.”

The findings are published in the journal Sleep Health.

COVID-19 Recovery Time: How Long Coronavirus Symptoms Last

Authors: By Jessica McBride Updated Apr 25, 2020 at 7:38pm

COVID-19 recovery time and symptoms can vary by person, but people who’ve had it often describe feeling like a mild cold is coming on before being hit with a fever, a dry cough, and shortness of breath. In short, it can be a slow-burning infection. However, others are asymptomatic or experience other symptoms, such as diarrhea, fatigue, a sore throat, a runny nose, and a headache. What is the recovery time for coronavirus?

Although the recovery time varies, reports show it’s a slow-moving illness that can take between two to six weeks to recover from, depending on how the body responds and the severity of illness. Experts say that it can take about a week of symptoms to know whether an infected person will end up in the hospital and worsen or start to get better. The World Health Organization reports:

The median time from onset to clinical recovery for mild cases is approximately 2 weeks and is 3-6 weeks for patients with severe or critical disease. Preliminary data suggests that the time period from onset to the development of severe disease, including hypoxia, is 1 week. Among patients who have died, the time from symptom onset to outcome ranges from 2-8 weeks.

You can read some real-life accounts of people who have had coronavirus later in this story as they describe how the virus recovery unfolded for them. What is the incubation period? “Because this coronavirus has just been discovered, the time from exposure to symptom onset (known as the incubation period) for most people has yet to be determined. Based on current information, symptoms could appear as soon as three days after exposure to as long as 13 days later. Recently published research found that on average, the incubation period is about five days,” says Harvard.

How soon into recovery can you stop isolating? According to WebMD, you should continue isolating until your fever has subsided for at least three days without medicine; your symptoms are better; and it’s been at least seven days since your symptoms started; or you’ve had two negative COVID-19 tests “24 hours apart.” According to John Hopkins Medicine, the virus usually starts in the throat, which is why it often produces a dry cough or sore throat. The problems really start if it migrates to the lungs. John Hopkins Medicine says that people with mild cases might recover in as little as a week.

According to NBC News, coronavirus is a virus with a “slow burn,” and experts say that, “very often,” the earliest symptoms are “minor physical complaints — slight cough, headache, low-grade fever,” that gradually get worse. Loss of taste and smell and red rimmed eyes have also emerged as possible symptoms of COVID-19. It often takes about a week after symptoms start to know whether the virus will worsen or the person will just get better, experts say. About half of the people who have COVID-19 never get symptoms at all, according to Fox News. That detail is based on research studies in Iceland, Vo, Italy, and the Diamond Princess cruise ship.

The World Health Organization reports that people with COVID-19 “generally develop signs and symptoms, including mild respiratory symptoms and fever, on an average of 5-6 days after infection (mean incubation period 5-6 days, range 1-14 days).”

About 80 percent of people end up with “mild disease” and recover, but this definition can include pneumonia. About 13.8 percent have severe disease, which includes shortness of breath and 6.1 percent are critical, suffering things like respiratory failure and septic shock, according to WHO.

The Centers for Disease Control and Prevention has now expanded its symptom list. Previously, the CDC listed only shortness of breath, a fever, and a dry cough as the key symptoms of coronavirus. Now the CDC lists the following:

People with COVID-19 have had a wide range of symptoms reported – ranging from mild symptoms to severe illness. These symptoms may appear 2-14 days after exposure to the virus:

Fever
Cough
Shortness of breath or difficulty breathing
Chills
Repeated shaking with chills
Muscle pain
Headache
Sore throat
New loss of taste or smell

Here’s what you need to know:


At About a Week In, Patients Tend to Get Better or End Up Hospitalized With Worsening Symptoms, Experts Say

Emerging 2019 Novel Coronavirus (2019-nCoV) PneumoniaEmerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia

It’s take about a week to know whether the body will kick COVID-19.

“Patients tend to have symptoms for about a week before either getting better, or getting really sick,” Dr. Joshua Denson, who works at Tulane Medical Center in New Orleans, told NBC. Sometimes, the network reported, coronavirus patients think they’re getting better until they take a sharp turn for the worse. Of course, most people do recover.

Diarrhea – and other digestive issues like vomiting, nausea, abdominal pain, and lack of appetite – have all been documented as symptoms seen in coronavirus patients. Diarrhea, vomiting and abdominal pain may be early symptoms of coronavirus in some cases.

“Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease,” researchers in a study in The American Journal of Gastroenterology found.

That study found that the early symptoms of coronavirus can be gastrointestinal, with respiratory symptoms coming later: “In some cases, the digestive symptoms, particularly diarrhea, can be the initial presentation of COVID-19, and may only later or never present with respiratory symptoms or fever.”

However, the three most prevalent symptoms are a fever, a dry cough, and shortness of breath.

Absence of those things doesn’t mean you don’t have it, though. The scientific community is just starting to understand COVID-19.

“The most common symptoms of COVID-19, the disease caused by the new coronavirus, are fever, cough and shortness of breath,” according to John Hopkins Medicine. “Some patients also have body aches, runny nose, sore throat or diarrhea. If you have a sore throat and think you have been exposed to the new coronavirus, contact a health care provider by phone and discuss your risk.”

The World Health Organization indicates that based on 55,924 laboratory confirmed cases, “typical signs and symptoms include: fever (87.9%), dry cough (67.7%), fatigue (38.1%), sputum production (33.4%), shortness of breath (18.6%), sore throat (13.9%), headache (13.6%), myalgiaor arthralgia (14.8%), chills(11.4%), nausea or vomiting (5.0%), nasal congestion (4.8%), diarrhea (3.7%), and hemoptysis (0.9%), and conjunctival congestion (0.80%).”

For More Information: https://heavy.com/news/2020/04/covid-19-recovery-time-how-long-symptoms-last/

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

These symptoms and risk factors may predict whether you could become a ‘COVID-19 long hauler,’ study suggests

Authors: Adrianna Rodriguez USA TODAY March 11, 2021

A new study suggests coronavirus symptoms felt in the first week of infection may be a predictor of how long they will last.

Patients with COVID-19 who felt more than five symptoms in their first week of illness were more likely to become a “COVID-19 long hauler,” which researchers qualified as having symptoms for longer than 28 days, according to the study published Wednesday in the peer-reviewed journal Nature Medicine.

The five symptoms experienced during the first week that were most predictive of becoming a long hauler were fatigue, headache, hoarse voice, muscle pain and difficulty breathing.

Researchers from King’s College London, Massachusetts General Hospital and Boston Children’s Hospital asked COVID-19 patients from the U.K., U.S. and Sweden to report their symptoms through a smartphone application from March to September 2020.

Out of more than 4,000 participants, about 13% of patients reported symptoms lasting more than 28 days, 4% for more than 8 weeks and 2% more than 12 weeks.

Out of the patients who reported symptoms for more than four weeks, “a third of those will have symptoms at 8 weeks and then a third of those at 12 weeks,” said study co-author Dr. Christina Astley, a physician scientist at Boston Children’s Hospital. “If you think about it, 1 in 20 people who have COVID-19 will have symptoms lasting 8 weeks or more.” 

The likelihood of having persistent symptoms was significantly associated with increasing age, rising from 9.9% of individuals 18 to 49, to 21.9% in those above 70. Anosmia, or the loss of smell, was the most common symptom in older age groups.

Women also were more likely to have long COVID-19 than men, with 14.9% of female study participants reporting symptoms 28 days after initial infection, compared with 9.5% of men.

While the study attempted to identify risk factors and markers that may indicate long COVID-19, doctors are finding it can happen to anyone at any age, said Dr. Michael Wechsler, a pulmonologist at National Jewish Health.

“It can happen in any age group, but it’s most alarming to younger people who are otherwise healthy and not used to these symptoms,” he said.

COVID long haulers:Dr. Anthony Fauci aims to answer ‘a lot of important questions’ in new nationwide initiative

The study found two main patterns among study participants. One group of COVID-19 long haulers exclusively reported fatigue, headache and upper respiratory issues, such as shortness of breath, sore throat, cough and loss of smell. However, a second group of long haulers had persistent multi-system complaints, such as a fever or gastrointestinal symptoms.

Weschler sees a wide array of symptoms in the clinic that caters to COVID-19 long haulers at National Jewish Health. Similar clinics have popped up in hospitals across the country to accommodate the growing number of COVID-19 patients who report symptoms months after recovery.

“Long COVID is common. It affects a large proportion of patients and has a wide distribution of symptoms,” he said. “It’s important to make people aware that all these different side effects and symptoms can occur.”

The study comes a few weeks after Dr. Anthony Fauci announced the U.S. government was launching nationwide initiative to study long COVID-19, which he called Post Acute Sequelae of SARS-CoV-2 (PASC).

A study published in JAMA Network Open on Feb. 19 found that about 30% of COVID-19 patients reported persistent symptoms as long as nine months after illness.

“(There are) a lot of important questions that are now unanswered that we hope with this series of initiatives we will ultimately answer,” he said during a White House briefing Feb. 24.

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:

The Epidemiology, Transmission, and Diagnosis of COVID-19

Authors: By: Neesha C. Siriwardane & Rodney Shackelford, DO, Ph.D. April 15, 2020

Introduction to COVID-19

Coronaviruses are enveloped single-stranded RNA viruses of the Coronaviridae family and order Nidovirales (1). The viruses are named for their “crown” of club-shaped S glycoprotein spikes, which surround the viruses and mediate viral attachment to host cell membranes (1-3). Coronaviruses are found in domestic and wild animals, and four coronaviruses commonly infect the human population, causing upper respiratory tract infections with mild common cold symptoms (1,4). Generally, animal coronaviruses do not spread within human populations, however rarely zoonotic coronaviruses evolve into strains that infect humans, often causing severe or fatal illnesses (4). Recently, three coronaviruses with zoonotic origins have entered the human population; severe acute respiratory syndrome coronavirus-2 (SARS) in 2003, Middle Eastern respiratory syndrome (MERS) in 2012, and most recently, coronavirus disease 2019 (COVID-19), also termed SARS-CoV-2, which the World Health Organization declared a Public Health Emergency of International Concern on January 31st, 2020 (4,5). 

COVID19 Biology, Spread, and Origin

COVID-19 replicates within epithelial cells, where the COVID-19 S glycoprotein attaches to the ACE2 receptor on type 2 pneumocytes and ciliated bronchial epithelial cells of the lungs. Following this, the virus enters the cells and rapidly uses host cell biochemical pathways to replicate viral proteins and RNA, which assemble into viruses that in turn infect other cells (3,5,6). Following these cycles of replication and re-infection, the infected cells show cytopathic changes, followed by various degrees of pulmonary inflammation, changes in cytokine expression, and disease symptoms (5-7). The ACE2 receptor also occurs throughout most of the gastrointestinal tract and a recent analysis of stool samples from COVID-19 patients revealed that up to 50% of those infected with the virus have a COVID-19 enteric infection (8).

COVID-19 was first identified on December 31st, 2020 in Wuhan China, when twenty-seven patients presented with pneumonia of unknown cause. Some of the patients worked in the Hunan seafood market, which sold both live and recently slaughtered wild animals (4,9).  Clusters of cases found in individuals in contact with the patients (family members and healthcare workers) indicated a human-to-human transmission pattern (9,10). Initial efforts to limit the spread of the virus were insufficient and the virus soon spread throughout China. Presently COVID-19 occurs in 175 countries, with 1,309,439 cases worldwide, with 72,638 deaths as of April 6th, 2020 (4). Presently, the most affected countries are the United States, Italy, Spain, and China, with the United States showing a rapid increase in cases, and as of April 6th, 2020 there are 351,890 COVID-19 infected, 10,377 dead, and 18,940 recovered (4).  In the US the first case presented on January 19th, 2020, when an otherwise healthy 35-year-old man presented to an urgent care clinic in Washington State with a four-day history of a persistent dry cough and a two-day history of nausea and vomiting.  The patient had a recent travel history to Wuhan, China. On January 20th, 2020 the patient tested positive for COVID-19.  The patient developed pneumonia and pulmonary infiltrates, and was treated with supplemental oxygen, vancomycin, and remdesivir. By day eight of hospitalization, the patient showed significant improvement (11). 

Sequence analyses of the COVID-19 genome revealed that it has a 96.2% similarity to a bat coronavirus collected in Yunnan province, China. These analyses furthermore showed no evidence that the virus is a laboratory construct (12-14). A recent sequence analysis also found that COVID-19 shows significant variations in its functional sites, and has evolved into two major types (termed L and S). The L type is more prevalent, is likely derived from the S type, and may be more aggressive and spread more easily (14,15). 

Transmission

While sequence analyses strongly suggest an initial animal-to-human transmission, COVID-19 is now a human-to-human contact spread worldwide pandemic (4,9-11). Three main transmission routes are identified; 1) transmission by respiratory droplets, 2) contract transmission, and 3) aerosol transmission (16). Transmission by droplets occurs when respiratory droplets are expelled by an infected individual by coughing and are inhaled or ingested by individuals in relatively close proximity.  Contact transmission occurs when respiratory droplets or secretions are deposited on a surface and another individual picks up the virus by touching the surface and transfers it to their face (nose, mouth, or eyes), propagating the infection. The exact time that COVID-19 remains infective on contaminated surfaces is unknown, although it may be up to several days (4,16). Aerosol transmission occurs when respiratory droplets from an infected individual mix with air and initiate an infection when inhaled (16). Transmission by respiratory droplets appears to be the most common mechanism for new infections and even normal breathing and speech can transmit the virus (4,16,17). The observation that COVID-19 can cause enteric infections also suggests that it may be spread by oral-fecal transmission; however, this has not been verified (8). A recent study has also demonstrated that about 30% of COIVID-19 patients present with diarrhea, with 20% having diarrhea as their first symptom. These patients are more likely to have COVID-19 positive stool upon testing and a longer, but less severe disease course (18).  Recently possible COVID-19 transmission from mother to newborns (vertical transmission) has been documented. The significance of this in terms of newborn health and possible birth defects is currently unknown (19). 

The basic reproductive number or R0, measures the expected number of cases generated by one infection case within a population where all the individuals can become infected. Any number over 1.0 means that the infection can propagate throughout a susceptible population (4). For COVID-19, this value appears to be between 2.2 and 4.6 (4,20,21). Unpublished studies have stated that the COVID10 R0 value may be as high as 6.6, however, these studies are still in peer review. 

COVID-19 Prevention

There is no vaccine available to prevent COVID-19 infection, and thus prevention presently centers on limiting COVID-19 exposures as much as possible within the general population (22). Recommendations to reduce transmission within community include; 1) hand hygiene with simultaneous avoidance of touching the face, 2) respiratory hygiene, 3) utilizing personal protective equipment (PPE) such as facemasks, 4) disinfecting surfaces and objects that are frequently touched, and 5) limiting social contacts, especially with infected individuals  (4,9,17,22). Hand hygiene includes frequent hand-washing with soap and water for twenty seconds, especially after contact with respiratory secretions produced by activities such as coughing or sneezing. When soap and water are unavailable, hand sanitizer that contains at least 60% alcohol is recommended (4,17,22). PPE such as N95 respirators are routinely used by healthcare workers during droplet precaution protocols when caring for patients with respiratory illnesses. One retrospective study done in Hunan, China demonstrated N95 masks were extremely efficient at preventing COVID-19 transfer from infected patients to healthcare workers (4,22-24). It is also likely that wearing some form of mask protection is useful to prevent COVID19 spread and is now recommended by the CDC (25). 

Although transmission of COVID-19 is primarily through respiratory droplets, well-studied human coronaviruses such as HCoV, SARS, and MERS coronaviruses have been determined to remain infectious on inanimate surfaces at room temperature for up to nine days. They are less likely to persist for this amount of time at a temperature of 30°C or more (26). Therefore, contaminated surfaces can remain a potential source of transmission. The Environmental Protection Agency has produced a database of appropriate agents for COVID-19 disinfection (27). Limiting social contact usually has three levels; 1) isolating infected individuals from the non-infected, 2) isolating individuals who are likely to have been exposed to the disease from those not exposed, and 3) social distancing. The later includes community containment, were all individuals limit their social interactions by avoiding group gatherings, school closures, social distancing, workplace distancing, and staying at home (28,29). In an adapted influenza epidemic simulation model, comparing scenarios with no intervention to social distancing and estimated a reduction of the number of infections by 99.3% (28). In a similar study, social distancing was estimated to be able to reduce COVID-19 infections by 92% (29). Presently, these measured are being applied in many countries throughout the world and have been shown to be at least partially effective if given sufficient time (4,17,30). Such measures proved effective during the 2003 SARS outbreak in Singapore (30). 

Symptoms, Clinical Findings, and Mortality 

On average COVID-19 symptoms appear 5.2 days following exposure and death fourteen days later, with these time periods being shorter in individuals 70-years-old or older (31,32). People of any age can be infected with COVID-19, although infections are uncommon in children and most common between the ages of 30-65 years, with men more affected than women (32,33). The symptoms vary from asymptomatic/paucisymptomatic to respiratory failure requiring mechanical ventilation, septic shock, multiple organ dysfunction, and death (4,9,32,33). The most common symptoms include a dry cough which can become productive as the illness progresses (76%), fever (98%), myalgia/fatigue (44%), dyspnea (55%), and pneumoniae (81%), with less common symptoms being headache, diarrhea (26%), and lymphopenia (44%) (4,32,33). Rare events such as COVID-19 acute hemorrhagic necrotizing encephalopathy have been documented and one paper describes conjunctivitis, including conjunctival hyperemia, chemosis, epiphora, or increased secretions in 30% of COVID-19 patients (34,35). Interestingly, about 30-60% of those infected with COVID-19 also experience a loss of their ability to taste and smell (36). 

The clinical features of COVID-19 include bilateral lung involvement showing patchy shadows or ground-glass opacities identified by chest X-ray or CT scanning (34). Patients can develop atypical pneumoniae with acute lung injury and acute respiratory distress syndrome (33). Additionally, elevations of aspartate aminotransferase and/or alanine aminotransferase (41%), C-reactive protein (86%), serum ferritin (63%), and increased pro-inflammatory cytokines, whose levels correlate positively with the severity of the symptoms (4,31-33,37-39).

About 81% of COVID-19 infections are mild and the patients make complete recoveries (38). Older patients and those with comorbidities such as diabetes, cardiovascular disease, hypertension, and chronic obstructive pulmonary disease have a more difficult clinical course (31-33,37-39). In one study, 72% of patients requiring ICU treatment had some of these concurrent comorbidities (40). According to the WHO 14% of COVID-19 cases are severe and require hospitalization, 5% are very severe and will require ICU care and likely ventilation, and 4% will die (41). Severity will be increased by older age and comorbidities (4,40,41). If effective treatments and vaccines are not found, the pandemic may cause slightly less than one-half billion deaths, or 6% of the world’s population (41). Since many individuals infected with COVID-19 appear to show no symptoms, the actual mortality rate of COIVD-19 is likely much less than 4% (42). An accurate understanding of the typical clinical course and mortality rate of COVID-19 will require time and large scale testing.         

COVID-19 Diagnosis

COVID-19 symptoms are nonspecific and a definitive diagnosis requires laboratory testing, combined with a thorough patient history.  Two common molecular diagnostic methods for COVID-19 are real-time reverse polymerase chain reaction (RT-PCR) and high-throughput whole-genome sequencing.  RT-PCR is used more often as it is cost more effective, less complex, and has a short turnaround time. Blood and respiratory secretions are analyzed, with bronchoalveolar lavage fluid giving the best test results (43). Although the technique has worked on stool samples, as yet stool is less often tested (8,43). RT-PCR involves the isolation and purification of the COVID-19 RNA, followed by using an enzyme called “reverse transcriptase” to copy the viral RNA into DNA. The DNA is amplified through multiple rounds of PCR using viral nucleic acid-specific DNA primer sequences. Allowing in a short time the COVID-19 genome ti be amplified millions of times and then easily analyzed (43). RT-PCR COVID-19 testing is FDA approved and the testing volume in the US is rapidly increasing (44,45). The FDA has also recently approved a COVID-19 diagnostic test that detects anti-COVID-19 IgM and IgG antibodies in patient serum, plasma, or venipuncture whole blood (43). As anti-COVID-19 antibody formation takes time, so a negative result does not completely preclude a COVID-19 infection, especially early infections. Last, as COVID-19 often causes bilateral pulmonary infiltrates, correlating diagnostic testing results with lung chest CT or X-ray results can be helpful (4,31-33,37-39).  

Testing for COVID-19 is based on a high clinical suspicion and current recommendations suggest testing patients with a fever and/or acute respiratory illness. These recommendations are categorized into priority levels, with high priority individuals being hospitalized patients and symptomatic healthcare facility workers. Low priority individuals include those with mild disease, asymptomatic healthcare workers, and symptomatic essential infrastructure workers. The latter group will receive testing as resources become available (41,46,47). 

COVID-19 Possible Treatments

Presently research on possible COVIS-19 infection treatments and vaccines are underway (48). At the writing of this article many different drugs are being examined, however any data supporting the use of any specific drug treating COVID-19 is thin as best. A few drugs that might have promise are:  

Hydroxychloroquine

Hydroxychloroquine has been used to treat malarial infections for seventy years and in cell cultures it has anti-viral effects against COVID-19 (49). In one small non-randomized clinical trial in France, twenty individuals infected with COVID-19 who received hydroxychloroquine showed a reduced COVID-19 viral load, as measured on nasopharyngeal viral carriage, compared to untreated controls (50). Six individuals who also received azithromycin with hydroxychloroquine had their viral load lessened further (50). In one small study in China, a similar drug (chloroquine) was superior in reducing COVID-19 viral levels in treated individuals compared to untreated control individuals (51).  These results are preliminary, but promising. 

Remdesivir

Remdesivir is a drug that showed value in treating patients infected with SARS (52). COVID-19 and SARS show about 80% sequence similarity and since Remdesivir has been used to treat SARS, it might have value in treating COVID-19 (52). These trials are underway (48). Remdesivir was also used to treat the first case of COIVD-19 identified within the US (11). There are many other drugs being examined to treat COVID-19 infections, however, the data on all of them is presently slight to none, and research has only begun. There is an enormous research effort underway, and progress should be rapid (48). 

Conclusion

Our understanding of COVID-19 is changing extremely rapidly and new findings come out daily. Combating COVID-19 effectively will require multiple steps; including slowing the spread of the virus through socially isolating and measures such as hand washing. The development of effective drug treatments and vaccines is already a priority and rapid progress is being made (48). Additionally, many areas of the world, such as South American and sub-Saharan Africa, will be affected by the COVID-19 pandemic and are likely to have their economies and healthcare systems put under extreme stress. Dealing with the healthcare crisis in these countries will be very difficult. Lastly, several recent viral pandemics (SARS, MERS, and COVID-19) have come from areas where wildlife is regularly traded, butchered, and eaten in conditions that favor the spread of dangerous viruses between species, and eventually into human populations. The prevention of new viral pandemics will require improved handling of wild species, better separation of wild animals from domestic animals, and better regulated and lowered trade in wild animals, such as bats, which are known to be a risk for carrying potentially deadly viruses to human populations (53). 

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Assessment of the Frequency and Variety of Persistent Symptoms Among Patients With COVID-19A Systematic Review

Authors: Tahmina Nasserie, MPH1Michael Hittle, BS1Steven N. Goodman, MD, MHS, PhD1 JAMA Netw Open. 2021;4(5):e2111417. doi:10.1001/jamanetworkopen.2021.11417 May 26, 2021

Key Points

Question  What are the frequency and variety of persistent symptoms after COVID-19 infection?

Findings  In this systematic review of 45 studies including 9751 participants with COVID-19, the median proportion of individuals who experienced at least 1 persistent symptom was 73%; symptoms occurring most frequently included shortness of breath or dyspnea, fatigue or exhaustion, and sleep disorders or insomnia. However, the studies were highly heterogeneous and needed longer follow-up and more standardized designs.

Meaning  This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life; however, methodological improvements are needed to reliably quantify these risks.Abstract

Importance  Infection with COVID-19 has been associated with long-term symptoms, but the frequency, variety, and severity of these complications are not well understood. Many published commentaries have proposed plans for pandemic control that are primarily based on mortality rates among older individuals without considering long-term morbidity among individuals of all ages. Reliable estimates of such morbidity are important for patient care, prognosis, and development of public health policy.

Objective  To conduct a systematic review of studies examining the frequency and variety of persistent symptoms after COVID-19 infection.

Evidence Review  A search of PubMed and Web of Science was conducted to identify studies published from January 1, 2020, to March 11, 2021, that examined persistent symptoms after COVID-19 infection. Persistent symptoms were defined as those persisting for at least 60 days after diagnosis, symptom onset, or hospitalization or at least 30 days after recovery from the acute illness or hospital discharge. Search terms included COVID-19SARS-CoV-2coronavirus2019-nCoVlong-termafter recoverylong-haulpersistentoutcomesymptomfollow-up, and longitudinal. All English-language articles that presented primary data from cohort studies that reported the prevalence of persistent symptoms among individuals with SARS-CoV-2 infection and that had clearly defined and sufficient follow-up were included. Case reports, case series, and studies that described symptoms only at the time of infection and/or hospitalization were excluded. A structured framework was applied to appraise study quality.

Findings  A total of 1974 records were identified; of those, 1247 article titles and abstracts were screened. After removal of duplicates and exclusions, 92 full-text articles were assessed for eligibility; 47 studies were deemed eligible, and 45 studies reporting 84 clinical signs or symptoms were included in the systematic review. Of 9751 total participants, 5266 (54.0%) were male; 30 of 45 studies reported mean or median ages younger than 60 years. Among 16 studies, most of which comprised participants who were previously hospitalized, the median proportion of individuals experiencing at least 1 persistent symptom was 72.5% (interquartile range [IQR], 55.0%-80.0%). Individual symptoms occurring most frequently included shortness of breath or dyspnea (26 studies; median frequency, 36.0%; IQR, 27.6%-50.0%), fatigue or exhaustion (25 studies; median frequency, 40.0%; IQR, 31.0%-57.0%), and sleep disorders or insomnia (8 studies; median 29.4%, IQR, 24.4%-33.0%). There were wide variations in the design and quality of the studies, which had implications for interpretation and often limited direct comparability and combinability. Major design differences included patient populations, definitions of time zero (ie, the beginning of the follow-up interval), follow-up lengths, and outcome definitions, including definitions of illness severity.

Conclusions and Relevance  This systematic review found that COVID-19 symptoms commonly persisted beyond the acute phase of infection, with implications for health-associated functioning and quality of life. Current studies of symptom persistence are highly heterogeneous, and future studies need longer follow-up, improved quality, and more standardized designs to reliably quantify risks.

For More Information: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780376

New Study Shows Insomnia More Common in COVID-19 Survivors

Updated April 14, 2021

Authors: Written by Elise Chahine

COVID-19 infection may have a large neurological and psychiatric impact on as many as one-third of its survivors.

A study published by Lancet Psychiatry finds that insomnia may be one of the most common neurological and psychiatric outcomes from COVID-19. Researchers evaluated the electronic health records of TriNetX, a global health research network, for approximately 236,000 patients, 10 years of age and older, who tested positive for COVID-19 from January 20, 2020 and were recorded as still alive on December 13, 2020 (see table for baseline characteristics). There was an estimated incidence of 14 neurological and psychiatric outcomes in the 6 months following a confirmed diagnosis of COVID-19, which included (but are not limited to) brain hemorrhage, stroke, muscle disease, dementia, mental health disorders, and insomnia. COVID-19 infection group’s outcomes were compared with flu and other respiratory tract infection groups’ outcomes.

Baseline Characteristics

CharacteristicsAll Patients
Cohort size236,379 (100.0%)
Age range, years26.3-65.7
Sex
  Male104,015 (44.0%)
  Female131,460 (55.6%)
  Other904 (0.4%)
Race
  White135,143 (57.2%)
  Black, African-American44,458 (18.8%)
  Unknown48,085 (20.3%)
Ethnicity
  Hispanic or Latino37,772 (16.0%)
  Not Hispanic or Latino134,075 (56.7%)
  Unknown64,532 (27.3%)

Researchers found that approximately 34% of their COVID patient population experienced at least 1 of the 14 neurological and/or psychiatric outcomes. While 5.4% of all patients in the study experienced insomnia, the number only increased with infection severity and need for hospitalization. With only 5.2% of non-hospitalized patients experiencing insomnia, the number jumps significantly upon hospital-entry to 6% and again to 7.5% and 10% for Intensive-Therapy-Unit–admitted and encephalopathy patients, respectively. It should be noted, this trend—an escalation in incidence with increased infection severity—was seen throughout the patient population despite neurological or psychiatric outcomes experienced.

Researchers speculate that some potential reasons for the neurological attack is viral invasion of the central nervous system, blood clotting disorders, and/or the toll immune response can take on our nervous system. The risks for these particular diagnoses may be small, but spread across a population can prove to have massive repercussions.

This study is further shedding light on the long-term implications COVID-19 will leave in its wake, plus the need for a more robust healthcare system to meet the needs of its population.