Virus World

The post-acute sequelae of SARS-CoV-2 infection (PASC) refers to a broad spectrum of symptoms and signs that are persistent, exacerbated or newly incident in the period after acute SARS-CoV-2 infection. Most studies have examined these conditions individually without providing evidence on co-occurring conditions. In this study, we leveraged the electronic health record data of two large cohorts, INSIGHT and OneFlorida+, from the national Patient-Centered Clinical Research Network. We created a development cohort from INSIGHT and a validation cohort from OneFlorida+ including 20,881 and 13,724 patients, respectively, who were SARS-CoV-2 infected, and we investigated their newly incident diagnoses 30–180 days after a documented SARS-CoV-2 infection.

Through machine learning analysis of over 137 symptoms and conditions, we identified four reproducible PASC subphenotypes, dominated by cardiac and renal (including 33.75% and 25.43% of the patients in the development and validation cohorts); respiratory, sleep and anxiety (32.75% and 38.48%); musculoskeletal and nervous system (23.37% and 23.35%); and digestive and respiratory system (10.14% and 12.74%) sequelae. These subphenotypes were associated with distinct patient demographics, underlying conditions before SARS-CoV-2 infection and acute infection phase severity. Our study provides insights into the heterogeneity of PASC and may inform stratified decision-making in the management of PASC conditions. Machine learning applied to electronic health records in two US cohorts from the RECOVER initiative identified four Long-COVID subphenotypes that differ in the involvement of organ systems, previous SARS-CoV-2 infection severity and underlying conditions.

Published in Nat. Medicine (DeC. 1, 2022):

https://doi.org/10.1038/s41591-022-02116-3 

All but 3 of 52  patients had lesions and rashes on their genitals or anal regions.  A new study published in The Lancet Infectious Diseases found that the clinical profile in recent monkeypox cases is different than in past events, with fatigue and fever less common and genital skin lesions more likely. This is the first study to look at these differences among cases in the current outbreak, and points to the important role sexual transmission among mostly men who have sex with men (MSM) has played in spreading monkeypox in non-endemic countries, many of which had never seen a monkeypox case before. 

Most had 5 or more new partners

In the study of UK cases, all 54 of the participants identified as MSM, and their median age was 41. The patients presented to UK sexual health clinics during a 2-week period in May, at the beginning of the global outbreak. None of the men had traveled to sub-Saharan Africa, but many reported recent European travel. Of the 54 men, 52 said they were not aware of being in recent contact with anyone with monkeypox.  Forty-seven of 52 men who answered questions on recent sexual history said they had at least one new sexual partner in the 3 weeks prior to symptoms, and 29 of 52 (55.8%) had more than 5 new partners in the 12 weeks prior to diagnosis. Almost all (49/52) patients presented with lesions and rashes on their genitals or anal regions. Only five patients required hospitalization, and no one died. One-quarter of the patients also were diagnosed with another sexually transmitted infection at the same time as monkeypox. "The commonly observed symptom of skin lesions in the anal and penile areas, and the fact that a quarter of the patients tested positive for gonorrhoea or chlamydia at the same time as the monkeypox infection, suggests that transmission of the monkeypox virus in this cohort is occurring from close skin-to-skin, for example in the context of sexual activity," said Ruth Byrne, MD, from the Chelsea & Westminster Hospital NHS Foundation Trust, in a press release on the study. Study authors also suggested that the primary symptom of genital rashes should be added to case definitions of monkeypox to more accurately identify symptomatic individuals. There are now more than 5,700 cases of monkeypox in non-endemic countries, mostly in Europe and North America.

Iowa, Wisconsin, Connecticut report first cases

US cases of monkeypox are continuing to grow, with Iowa, Wisconsin, and Connecticut reporting their first cases of the virus. According to the Centers for Disease Control and Prevention, the country has 460 cases in 32 states. In Iowa, health officials said the patient likely acquired the virus when traveling internationally. In Connecticut, health officials confirmed the patient was a man in his 40s from New Haven. California has the most the most cases in the country, with 95, followed by 90 cases in New York. Illinois has 53 cases.

Research cited published in The Lancet Infectious Diseases (July 1, 2022): 

https://doi.org/10.1016/S1473-3099(22)00411-X

A South African doctor who was one of the first to suspect a different coronavirus strain among patients said on Sunday that symptoms of the Omicron variant were so far mild and could be treated at home.

JOHANNESBURG, Nov 28 (Reuters) - A South African doctor who was one of the first to suspect a different coronavirus strain among patients said on Sunday that symptoms of the Omicron variant were so far mild and could be treated at home. Dr. Angelique Coetzee, a private practitioner and chair of South African Medical Association, told Reuters that on Nov. 18 she noticed seven patients at her clinic who had symptoms different from the dominant Delta variant, albeit "very mild". Now designated Omicron by the World Health Organization, the variant was detected and announced by South Africa's National Institute of Communicable Diseases (NICD) on Nov. 25 from samples taken from a laboratory from Nov. 14 to Nov. 16. Coetzee said a patient on Nov. 18 reported at her clinic being "extremely fatigued" for two days with body aches and headache. "Symptoms at that stage was very much related to normal viral infection. And because we haven't seen COVID-19 for the past eight to 10 weeks, we decided to test," she said, adding that the patient and his family turned out to be positive. On the same day, more patients came in with similar symptoms, which was when she realised there was "something else going on." Since then, she's seen two to three patients a day. 

"We have seen a lot of Delta patients during the third wave. And this doesn't fit in the clinical picture," she said, adding she alerted NICD on the same day with the clinical results. "Most of them are seeing very, very mild symptoms and none of them so far have admitted patients to surgeries. We have been able to treat these patients conservatively at home," she said. Coetzee, who is also on the Ministerial Advisory Committee on Vaccines, said unlike the Delta so far patients have not reported loss of smell or taste and there has been no major drop in oxygen levels with the new variant. Her experience so far has been that the variant is affecting people who are 40 or younger. Almost half of the patients with Omicron symptoms that she treated were not vaccinated. "The most predominant clinical complaint is severe fatigue for one or two days. With them, the headache and the body aches and pain." The news of the new variant emerging from South Africa prompted a swift reaction from several countries, including Britain, which on Friday imposed a travel ban on several southern African countries with immediate effect, a decision South Africa has strongly contested.  Since Friday, many countries have also banned air travel to and from South Africa, including the United States, other European countries, and some Asian nations.

Purpose: To develop a reliable tool that predicts which patients are most likely to be COVID-19 positive and which ones have an increased risk of hospitalization. Methods: From February 2020 to April 2021, trained nurses recorded age, gender, and symptoms in an outpatient COVID-19 testing center. All positive patients were followed up by phone for 14 days or until symptom-free. We calculated the symptoms odds ratio for positive results and hospitalization and proposed a random forest machine-learning model to predict positive testing. Results: A total of 8,998 patients over 16 years old underwent COVID-19 RT-PCR, with 1,914 (21.3%) positives. Fifty patients needed hospitalization (2.6% of positives), and three died (0.15%). Most common symptoms were: cough, headache, sore throat, coryza, fever, myalgia (57%, 51%, 44%, 36%, 35%, 27%, respectively). Cough, fever, and myalgia predicted positive COVID-19 test, while others behaved as protective factors. The best predictors of positivity were fever plus anosmia/ageusia (OR=6.31), and cough plus anosmia/ageusia (OR=5.82), both p<0.0001. Our random forest model had an ROC-AUC of 0.72 (specificity=0.70, sensitivity=0.61, PPV=0.38, NPV=0.86). Having steady fever during the first days of infection and persistent dyspnea increased the risk of hospitalization (OR=6.66, p<0.0001 and OR=3.13, p=0.003, respectively), while anosmia-ageusia (OR=0.36, p=0.009) and coryza (OR=0.31, p=0.014) were protective. Conclusion: Present study and algorithm may help identify patients at higher risk of having SARS-COV-2 (online calculator http://wdchealth.covid-map.com/shiny/calculator/), and also disease severity and hospitalization based on symptoms presence, pattern, and duration, which can help physicians and health care providers.

Available as Preprint in medRxiv (August 10, 2021):

https://doi.org/10.1101/2021.08.09.21261729 

An analysis of Ebola survivors in Sierra Leone revealed that patients with post-Ebola syndrome experience clusters of symptoms that occur together, including some with a seemingly rheumatologic pattern of disease, researchers reported.“Ebola survivors have a broad array of symptoms that fall into distinct patterns. One of these patterns resembles rheumatologic disease and may be related to gut dysfunction,” Sarah Talia Himmelfarb, MD, a resident in internal medicine and pediatrics at Tulane University School of Medicine, explained to Healio. Research has shown that Ebola survivors may face long-term health effects from the illness. “To date,” Himmelfarb said, “several studies have been performed to determine if specific markers of inflammation are associated with post-Ebola syndrome. No marker has been identified when looking at survivors as a homogeneous group.” To identify patterns within the variety of symptoms experienced by Ebola survivors, Himmelfarb and colleagues identified survivors in Eastern Sierra Leone through the Sierra Leone Association of Ebola Survivors and household contacts of survivors and recruited them for a study. Himmelfarb presented findings from the study at IDWeek. Participants from both groups received a questionnaire regarding self-reported symptoms and underwent a physical exam. The researchers compared symptoms between the groups and analyzed correlations between clusters.

“Our motivation in doing this was to see if any patterns fit known disease processes,” Himmelfarb said. “In particular, we wanted to investigate the possibility that they fit the pattern of a rheumatologic or autoimmune disease. This would help us better understand this poorly characterized syndrome and might help lead to therapies for those who suffer from it.” Between March 2016 and January 2019, 375 Ebola survivors and 1,040 contacts were enrolled in the study. According to Himmelfarb and colleagues, at the time of enrollment, Ebola survivors across all age groups reported significantly more symptoms than contacts in all categories. The researchers identified six symptom clusters “representing distinct organ systems” and two general phenotypes with or without rheumatologic symptoms. According to the study, clusters including rheumatologic symptoms were correlated with one another (r = 0.63) but not with other clusters (r < 0.35). Additionally, ophthalmologic/auditory symptoms were moderately correlated with the nonrheumatologic clusters (r > 0.5), whereas psychologic/neurologic, cardiac/gastrointestinal and constitutional clusters correlated with one another (r >0.6) in all cases. 

After mapping the symptom clusters, the researchers determined that each symptom cluster was separated from the rest, particularly the phenotypes with rheumatologic symptoms.  The group of survivors with the seemingly rheumatologic pattern of disease complained of symptoms that included joint pain and decreased range of motion, Himmelfarb said. This group overlapped with a group with gastroenterological symptoms, such as abdominal tenderness. “An intriguing possibility is that inflammation stemming from impaired gut barrier, as was detected in a previous study, may be an etiologic cause of this group of symptoms,” Himmelfarb said. “This work has significance for the thousands of Ebola survivors who emerged from the 2014-2016 epidemic in Western Africa. It also contributes a small but growing body of knowledge of post-viral sequelae. This field has only become more relevant in the age of COVID-19.”

How long could I be contagious before a positive virus test? Studies have shown that people may be contagious for about two days before developing COVID-19 symptoms. In fact, right before developing symptoms is when people are likely the most contagious, said Dr. Werner Bischoff, an infectious disease specialist at Wake Forest University. People who never develop symptoms can spread infection, too. That’s a problem because many people would never seek testing unless they developed symptoms or knew they’d been exposed. But there’s a more complicated part to this question: What if someone knows they were exposed but their virus test comes back negative -- could they still be contagious? Maybe.

A negative test within less than seven days after exposure “is a very, very poor indicator of whether you have virus on board,” said Dr. Alan Wells of the University of Pittsburgh Medical Center. Some tests are less accurate than others, and you have to factor in the incubation period, he said.  A negative test between seven and 10 days of exposure is a better indicator, Wells said, but even then some people might not test positive until later. “That is why if you have had a credible exposure, you should wear a mask and you should self-quarantine if there’s any question,” he said.

Researchers at the top-ranked hospital in Boston compared search interest in loss of taste and appetite, and diarrhea with the reported incidence of Covid-19 in 15 U.S. states from January 20 to April 20. Using Alphabet Inc.s Google Trends online tool, they found the volume of searches correlated most strongly with cases in New York, New Jersey, California, Massachusetts and Illinois - states with high disease burden - three to four weeks later. Internet searches on gastrointestinal symptoms predicted a rise in Covid-19 cases weeks later, researchers at Massachusetts General Hospital found, demonstrating a novel early warning system for hot spots of the pandemic disease. 

The research, published in the journal Clinical Gastroenterology and Hepatology, showed that the same approach used to monitor pandemic influenza trends more than a decade ago could be deployed for the coronavirus, the hospital said in a report this month. Patients with Covid-19 often report gastrointestinal symptoms, such as abdominal pain and diarrhea, sparking interest in conducting the study. “Our data underscore the importance of GI symptoms as a potential harbinger of Covid-19 infection and suggests that Google Trends may be a valuable tool for prediction of pandemics with GI manifestations,” Kyle Staller, a gastroenterologist and the director of Mass General’s gastrointestinal motility laboratory, and colleagues wrote in the study. Scientists are also testing for traces of the coronavirus in wastewater to identify places where Covid-19 is spreading.

British scientists analysing data from a widely-used COVID-19 symptom-tracking app have found there are six distinct types of the disease, each distinguished by a cluster of symptoms. A King’s College London team found that the six types also correlated with levels of severity of infection, and with the likelihood of a patient needing help with breathing - such as oxygen or ventilator treatment - if they are hospitalised. The findings could help doctors to predict which COVID-19 patients are most at risk and likely to need hospital care in future waves of the epidemic.

“If you can predict who these people are at Day Five, you have time to give them support and early interventions such as monitoring blood oxygen and sugar levels, and ensuring they are properly hydrated,” said Claire Steves, a doctor who co-led the study. Besides cough, fever and loss of smell - often highlighted as three key symptoms of COVID-19 - the app data showed others including headaches, muscle pains, fatigue, diarrhoea, confusion, loss of appetite and shortness of breath. The outcomes also varied significantly; some got mild, flu-like symptoms or a rash and others suffered acute symptoms or died. The study, released online on June 16 but not peer-reviewed by independent scientists, described the six COVID-19 types as:

1 ‘Flu-like’ with no fever: Headache, loss of smell, muscle pains, cough, sore throat, chest pain, no fever.

2 ‘Flu-like’ with fever: Headache, loss of smell, cough, sore throat, hoarseness, fever, loss of appetite.

3 Gastrointestinal: Headache, loss of smell, loss of appetite, diarrhoea, sore throat, chest pain, no cough.

4 Severe level one, fatigue: Headache, loss of smell, cough, fever, hoarseness, chest pain, fatigue.

My first Covid-19 symptoms appeared March 14. More than 100 days later, Covid-19 is still with me. Some days I wonder if it will ever leave. In the early days, as my symptoms fluctuated, I was determined not to go to the emergency department or urgent care because it seemed like there were too many people who needed the help more than I did. Maybe I was especially sensitive to overcrowding in emergency departments because I’m a physician. But it turns out that this strategy was a common one. In New York City, where I live and work, there were more than 5,000 excess deaths not directly linked to Covid-19 between March 11 and May 2, likely because people were delaying care or not going to emergency departments or urgent care due to fear of contracting Covid-19 or oversaturating the medical system.

I did eventually go to the emergency department one day when the abdominal pain and nausea were severe. Routine testing showed that the level of liver enzymes in my blood was higher than it should have been, but not much more, and I was sent home. Once day 14 had passed, my fear of an impending respiratory collapse turned into an uncertainty about the trajectory of my disease and a desperation for answers. I contacted my doctors regularly, hoping their responses would bring relief in the form of some intervention. Yet most of their efforts did little to significantly change the course of my symptoms.....

Dermatologists say the lesions should prompt testing for the virus, even though many patients have no other symptoms. Before the coronavirus outbreak, Dr. Lindy Fox, a dermatologist in San Francisco, used to see four or five patients a year with chilblains — painful red or purple lesions that typically emerge on fingers or toes in the winter. Over the past few weeks, she has seen dozens. “All of a sudden, we are inundated with toes,” said Dr. Fox, who practices at the University of California, San Francisco. “I’ve got clinics filled with people coming in with new toe lesions. And it’s not people who had chilblains before — they’ve never had anything like this.”

It’s also not the time of year for chilblains, which are caused by inflammation in small blood vessels in reaction to cold or damp conditions. “Usually, we see it in the dead of winter,” Dr. Fox said. Dr. Fox is not the only one deluged with cases. In Boston, Dr. Esther Freeman, director of global health dermatology at the Massachusetts General Hospital, said her telemedicine clinic is also “completely full of toes. I had to add extra clinical sessions, just to take care of toe consults. People are very concerned.” The lesions are emerging as yet another telltale symptom of infection with the new coronavirus. The most prominent signs are a dry cough and shortness of breath, but the virus has been linked to a string of unusual and diverse effects, like mental confusion and a diminished sense of smell. Federal health officials do not include toe lesions in the list of coronavirus symptoms, but some dermatologists are pushing for a change, saying so-called Covid toe should be sufficient grounds for testing. (Covid-19 is the name of the illness caused by the coronavirus.)

Several medical papers from Spain, Belgium and Italy described a surge in complaints about painful lesions on patients’ toes, Achilles' heels and soles of the feet; whether the patients were infected was not always clear, because they were otherwise healthy and testing was limited. Most cases have been reported in children, teens and young adults, and some experts say they may reflect a healthy immune response to the virus. “The most important message to the public is not to panic — most of the patients we are seeing with these lesions are doing extremely well,” Dr. Freeman said.  “They’re having what we call a benign clinical course. They’re staying home, they’re getting better, the toe lesions are going away.”...

BA.5 has become dominant in the U.S.  In June, the Centers for Disease Control and Prevention reported that the Omicron subvariants BA.4 and BA.5 had become dominant in the U.S. The agency revised that statement on July 5 to say that BA.5 made up over half of new cases in the country. Experts said that, in general, these subvariants do not have markedly divergent symptoms from earlier versions of Omicron. People infected with BA.4 and BA.5 may develop a cough, runny nose, sore throat, fatigue, headaches and muscle pains. However, they are less likely to lose their senses of taste and smell, or to experience shortness of breath, as compared with those infected with Delta or other variants of the coronavirus, said Dr. Peter Chin-Hong, an infectious disease specialist at the University of California, San Francisco. Dr. Joseph Khabbaza, a pulmonary and critical care physician at Cleveland Clinic, said people tend to experience upper respiratory symptoms “from the vocal cords to the tip of the nose.” Anecdotally, he said, he has seen more patients with painful sinus congestion and severe sore throats who have tested positive for Covid-19 while BA.4 and BA.5 have been circulating. Some of them thought they had strep throat because they were in so much pain, he said.

Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study has been monitoring the spread and clinical manifestation of SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell and taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and induced changes in daily activities will become increasingly important.

Preprint in medRxiv (May 23, 2022):

https://doi.org/10.1101/2022.05.21.22275368 

Children are almost as likely as adults to become infected with coronavirus, but they are less likely to have symptoms, according to a new study published Friday.  The new study, published in the journal JAMA Pediatrics, found adults and children living in Utah and New York City shared similar risks of becoming infected with coronavirus. But kids only had symptoms about half the time. "The study demonstrates that all along, children of all ages including infants and toddlers have had a similar risk of SARS- CoV-2 infection compared with adults," Dr. Flor Munoz, a pediatric infectious disease specialist at Texas Children's Hospital and associate professor of pediatrics at Baylor College of Medicine, wrote in an accompanying editorial. SARS-CoV-2 is the name of the coronavirus that causes Covid-19.  "The fact that children, and especially young children, can transmit SARS-CoV-2 is now established and more clearly understood," wrote Munoz, who was not involved in the study. She added that the new findings should be considered in pandemic control efforts as well as vaccine and therapeutics research.

These findings were published just a day after the companies Pfizer and BioNTech officially requested emergency use authorization from the US Food and Drug Administration for their Covid-19 vaccine, at a smaller dosage, in children ages 5 to 11.  The new research, conducted from September 2020 through April 2021, included data on 1,236 people from 310 different households with one or more children in New York City, and certain counties throughout Utah. Dr. Fatimah Dawood of the US Centers for Disease Control and Prevention and colleagues took a close look at the incidence of Covid-19 and found that among households with one or more people infected, the mean infection risk within those households was 52%, adding to the evidence that households remain a common place that the virus spreads.

Original findings published in JAMA Pediatrics (Oct. 8, 2021):

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2785007 

Two-thirds of those in the study sought medical care a month to six months afterward, and about two-thirds of those who sought care were found to have an entirely new medical condition.  Most adults who test positive for the coronavirus don’t require hospitalization but tend to seek medical care in subsequent months, and two-thirds of those who do are told they have a health condition they did not have before. These are the findings of a study conducted by investigators from the Centers for Disease Control and Prevention and Kaiser Permanente, which included some 3,171 members of the Kaiser Permanente Georgia integrated health care system. More than half were Black. The message for patients is that even for those who have had only mild Covid-19, “it’s possible you may experience new or persistent symptoms months after the initial diagnosis,” said Dr. Alfonso C. Hernandez-Romieu, an infectious disease specialist with the C.D.C., and the study’s lead author. “And it’s important for people to make sure they’re going to their clinicians,” he said, to express their concerns. “It’s equally important,” he added, “for clinicians to acknowledge that there may be these long-term effects and to really make sure they’re validating patients, treating them with empathy and trying to help them in the best way possible.”

Greatest risk of passing the virus on is in the first few days of having symptoms, analysis suggests. The research indicates patients had the highest levels of virus early on in their illness and "live" virus, capable of replicating, was found up to nine days after symptoms began. UK scientists say their study emphasises early isolation is critical to stopping spread. 

Peak Infectivity

How infectious individuals are depends on many factors, including how much viable virus (essentially, virus that is able to replicate) they are carrying and the amount of virus they have in their bodies. Some reports have shown people are most infectious just before they have symptoms and in the first week of having the virus. Scientists examined 79 global studies on Covid-19, involving symptomatic people in hospitals who had already tested positive for the virus. Researchers were able to identify and replicate viable virus from throat samples taken up to nine days after infections started. And they found the amount of viral RNA particles (fragments of genetic material from the virus) in people's throat samples peaked at the time symptoms began or within five days.  Meanwhile, inactive viral RNA fragments were still found in nose and throat samples on average up to 17 days after symptoms started.

The hospitalized patients showed signs of deteriorating neurological function, ranging from confusion to coma-like unresponsiveness, new research indicates. Nearly a third of hospitalized Covid-19 patients experienced some type of altered mental function — ranging from confusion to delirium to unresponsiveness — in the largest study to date of neurological symptoms among coronavirus patients in an American hospital system. And patients with altered mental function had significantly worse medical outcomes, according to the study, published on Monday in Annals of Clinical and Translational Neurology. The study looked at the records of the first 509 coronavirus patients hospitalized, from March 5 to April 6, at 10 hospitals in the Northwestern Medicine health system in the Chicago area. These patients stayed three times as long in the hospital as patients without altered mental function. After they were discharged, only 32 percent of the patients with altered mental function were able to handle routine daily activities like cooking and paying bills, said Dr. Igor Koralnik, the senior author of the study and chief of neuro-infectious disease and global neurology at Northwestern Medicine. In contrast, 89 percent of patients without altered mental function were able to manage such activities without assistance.

Patients with altered mental function — the medical term is encephalopathy — were also nearly seven times as likely to die as those who did not have that type of problem. “Encephalopathy is a generic term meaning something’s wrong with the brain,” Dr. Koralnik said. The description can include problems with attention and concentration, loss of short-term memory, disorientation, stupor and “profound unresponsiveness” or a coma-like level of consciousness.  “Encephalopathy was associated with the worst clinical outcomes in terms of ability to take care of their own affairs after leaving the hospital, and we also see it’s associated with higher mortality, independent of severity of their respiratory disease,” he said. The researchers did not identify a cause for the encephalopathy, which can occur with other diseases, especially in older patients, and can be triggered by several different factors including inflammation and effects on blood circulation, said Dr. Koralnik, who also oversees the Neuro Covid-19 Clinic at Northwestern Memorial Hospital. There is very little evidence so far that the virus directly attacks brain cells, and most experts say neurological effects are probably triggered by inflammatory and immune system responses that often affect other organs, as well as the brain.

“This paper indicates, importantly, that in-hospital encephalopathy may be a predictor for poorer outcomes,” said Dr. Serena Spudich, chief of neurological infections and global neurology at Yale School of Medicine, who was not involved in the study. That finding would also suggest that patients with altered mental function in the hospital “might benefit from closer post-discharge monitoring or rehabilitation,” she added. In the study, the 162 patients with encephalopathy were more likely to be older and male. They were also more likely to have underlying medical conditions, including a history of any neurological disorder, cancer, cerebrovascular disease, chronic kidney disease, diabetes, high cholesterol, heart failure, hypertension or smoking. Some experts said that President Trump, who was hospitalized with Covid at Walter Reed military hospital beginning on Friday, is of the age and gender of the patients in the study who were more likely to develop altered mental function and therefore could be at higher risk for such symptoms. He also has a history of high cholesterol, one of the pre-existing conditions that appear to increase risk. But the president’s doctors have given no indication that he has had any neurological symptoms; the White House had released videos of him talking to the public about how well he was doing. And Mr. Trump returned to the White House on Monday evening....

Study published in Annals Clinica and  Translational Neurology (October 5, 2020):

https://doi.org/10.1002/acn3.51210

Fever, runny nose, headache? Lost your sense of taste or smell? Your guide to differentiating between the three illnesses. With winter approaching, the UK is entering the traditional seasons for colds and flu, with the additional complication this year that symptoms of those two illnesses can be broadly similar to those experienced by people who have caught the coronavirus and may be at risk of spreading it. The NHS in England has produced a guide to differentiate between the three types of illnesses, which health experts hope will make it clearer to people whether they have an illness they would have most likely brushed aside last year, but which this year might lead them to think they need to self-isolate or seek to have a coronavirus test.

Coronavirus or Covid-19

The most common symptoms of coronavirus or Covid-19 are a fever – a temperature of 37.8C (100F) – a new persistent cough (usually dry), and a loss of their sense of taste and/or smell. Patients may also sometimes suffer from fatigue, aches and pains, sore throat, headaches and shortness of breath. Diarrhoea and a runny or stuffy nose are rare. The NHS says symptoms can range from mild to severe.

Cold

The most common symptoms of a cold are sneezing, aches and pains, a runny or stuffy nose and sore throat. A mild cough can be experienced. There is sometimes fatigue, and it is rare to experience a fever or headaches. Colds do not cause diarrhoea. The NHS states that with a cold there is usually a gradual onset of symptoms

Flu

Flu most commonly consists of a fever, fatigue, a dry cough, aches and pains and headaches. Patients will sometimes experience a runny or stuffy nose or a sore throat. Diarrhoea can sometimes occur in children. There is no sneezing or shortness of breath with flu, and the NHS notes there is usually a rapid onset of symptoms.

The research at Bristol's Southmead Hospital is part of a project looking into the longer-term effects of coronavirus. A total of 81 patients out of 110 discharged from Southmead Hospital in Bristol were still experiencing symptoms from the virus, including breathlessness, excessive fatigue and muscle aches, after 12 weeks. Many were struggling to carry out daily tasks such as washing, dressing or going back to work, the study found. The majority of patients reported improvements in the initial symptoms of fever, cough and loss of sense of smell, and most had no evidence of lung scarring or reductions in lung function. The findings are part of North Bristol NHS Trust's Discover project, which is studying the longer-term effects of coronavirus - so-called Long COVID. A total of 163 patients with coronavirus were recruited to the study, and of those 19 died. The remainder were invited for a three-month check-up and 110 attended. Most (74%) had persistent symptoms - notably breathlessness and excessive fatigue - with reduced quality of life.

Only patients who required oxygen therapy in hospital had abnormal radiology, clinical examination or spirometry - a test used to assess how well your lungs work - at the follow-up appointment. An intensive care doctor told Sky News in June that he was still suffering COVID-19 symptoms three months after contracting the disease. Dr Jake Suett, 31, had no underlying health conditions but was still suffering chest pain, breathlessness, blurred vision, memory loss, a high temperature, concentration problems. The doctor, who works for the NHS in Norfolk, said at the time: "I still get out of breath doing the washing up or walking around the house. "I spent three days just gasping for breath in bed, I really thought I was going to die, it was very distressing. "Things have improved since then, but not much and only very, very slowly. I've had gastrointestinal symptoms and shooting pains in my hands and feet too." MPs from the All Party Parliamentary Group on coronavirus heard earlier this month from previously fit people whose lives have been turned upside down by a host of symptoms.

Claire Hastie, a member of a Long COVID support group on Facebook, described how she used to cycle 13 miles to work but can no longer walk 13 metres and is now largely confined to a wheelchair with her children providing much of her care. The research at Southmead Hospital is due to continue, with researchers collaborating with the University of Bristol to look at the participant blood tests, rehabilitation therapies and psychological support. Dr Rebecca Smith, from North Bristol NHS Trust, said: "There's still so much we don't know about the long-term effects of coronavirus, but this study has given us vital new insight into what challenges patients may face in their recovery and will help us prepare for those needs." 

Morbidity can happen over a long-term period, so it is a harder variable to study and track in the early stages of a pandemic than death. Anecdotal reports and early data, though, show that Covid-19 morbidity may be a very real concern. According to a publication in JAMA, which followed several  Covid-19 patients over several weeks, many had long-lasting symptoms and impairments (including headaches and debilitating fatigue) that didn’t resolve when their active infection cleared.

All of these cases were considered “mild” and didn’t result in the use of a ventilator or a stay in the ICU. And they occurred in people from a variety of age groups, not only older adults and the infirm. Yet despite these “low risk” factors, patients were still experiencing major impacts from the disease months after contracting it. A handful of studies about Covid-19 (as well as scholarship on previous coronaviruses) bears this out. Covid-19 infection can have long-term impacts on the lungs, heart, immune system, and even the brain. These include an increased risk for heart attacks, future respiratory infections (including more severe cases of flu), and neurological impacts like cognitive impairment.

Original study published in JAMA (July 9, 2020):

https://doi.org/10.1001/jama.2020.12603

Recent reports suggest that sudden smell loss might be a symptom of SARS-CoV-2 infection. The aim of this study was to investigate the frequency of olfactory loss in an out-patient population who presented to a coronavirus testing center during a 2-week period and to evaluate the diagnostic value of the symptom sudden smell loss for screening procedures. 

In this cross-sectional controlled cohort study, 500 patients who presented with symptoms of a common cold to a corona testing center and fulfilled corona testing criteria, completed a standardized diagnostic questionnaire which included the patients main symptoms, time course and an additional self-assessment of the patients current smell, taste function and nasal breathing compared to the level before onset of symptoms. 

Out of the 500 patients, 69 presented with olfactory loss. Twenty-two of them subsequently tested positive for SARS-CoV-2. Only twelve out of the patients without olfactory loss tested positive, resulting in a frequency of 64.7% for the symptom sudden smell loss in COVID-19 patients. Compared to COVID-19 patients without smell loss, they were significantly younger and less severely affected. Changes in nasal airflow were significantly more pronounced in SARS-CoV-2 negative patients with olfactory complaints compared to the patients with smell loss who were tested positive for SARS-CoV-2. By excluding patients with a blocked nose, the symptom sudden smell loss can be attested a high specificity (97%) and a sensitivity of 65% with a PPV of 63% and NPV of 97% for COVID-19.

Considering the high frequency of smell loss in non-hospitalized COVID-19 patients, acute olfactory impairment should be included in the WHO symptoms list and should be recognized as an early symptom of the disease. In contrast to other acute viral smell impairment, COVID-19 associated smell loss seems to be only rarely accompanied by a severely blocked nose.

Preprint Available at medRxiv (April 27.2020):

https://www.medrxiv.org/content/10.1101/2020.04.27.20081356v1