The mild disease does not lead to substantial long-term illness in most infected individuals, say researchers.

Most symptoms or conditions that develop after mild covid-19 infection linger for several months but return to normal within a year finds a large study from Israel published by The BMJ today.

In particular, vaccinated people were at lower risk of breathing difficulties – the most common effect to develop after mild infection – than unvaccinated people.

These findings suggest that, although the long covid phenomenon has been feared and discussed since the beginning of the pandemic, the vast majority of mild disease cases do not suffer serious or chronic long term illness, say the researchers.

Long covid is defined as symptoms persisting or new symptoms appearing more than four weeks after initial infection. In March 2022, an estimated 1.5 million people in the UK (2.4% of the population) reported long covid symptoms, mainly fatigue, shortness of breath, loss of smell, loss of taste, and difficulty concentrating.

But the clinical effects of long covid one year after mild infection and their association with age, sex, covid-19 variants, and vaccination status are still unclear.

To address this, researchers compared the health of uninfected individuals with those who had recovered from mild covid-19 for a year after infection.

They used electronic records of a large public healthcare organisation in Israel, in which almost 2 million members were tested for covid-19 between 1 March 2020 and 1 October 2021. Over 70 long covid conditions were analysed in a group of infected and matched uninfected members (average age 25 years; 51% female).

They compared conditions in unvaccinated people, with and without covid-19 infection, controlling for age, sex and covid-19 variants, during early (30-180 days) and late (180-360 days) time periods after infection. Conditions in vaccinated versus unvaccinated people with covid-19 were also compared over the same time periods.

To ensure only mild disease was assessed, they excluded patients admitted to hospital with more serious illness. Other potentially influential factors, such as alcohol intake, smoking status, socioeconomic level, and a range of pre-existing chronic conditions were also taken into account.

Covid-19 infection was significantly associated with increased risks of several conditions including loss of smell and taste, concentration and memory impairment, breathing difficulties, weakness, palpitations, streptococcal tonsillitis and dizziness in both early and late time periods, while hair loss, chest pain, cough, muscle aches and pains and respiratory disorders resolved in the late period.

For example, compared with non-infected people, mild covid-19 infection was associated with a 4.5-fold higher risk of smell and taste loss (an additional 20 people per 10,000) in the early period and an almost 3-fold higher risk (11 per 10,000 people) in the late period. 

The overall burden of conditions after infection across the 12-month study period was highest for weakness (an additional 136 people per 10,000) and breathing difficulties (107 per 10,000).

When conditions were assessed by age, breathing difficulties were the most common, appearing in five of the six age groups but remaining persistent throughout the first year post-infection in the 19-40, 41-60, and over 60 years age groups. 

Weakness appeared in four of the six age groups and remained persistent in the late phase only in the 19-40 and 41-60 age groups.

Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings were similar across the wild-type, Alpha and Delta covid-19 variants.

Vaccinated people who became infected had a lower risk of breathing difficulties and similar risk for other conditions compared with unvaccinated infected patients.

The researchers point to some limitations, such as incomplete measurement within medical records, so data might not fully reflect diagnoses and outcomes reported. And they can’t rule out the possibility that covid-19 patients may use healthcare services more frequently, resulting in higher reporting and increased screening for potential covid-related outcomes in these patients.

Nevertheless, this was a large detailed analysis of health records across a diverse population, representing one of the longest follow-up studies in patients with mild covid-19 to date. And findings should apply to similar western populations worldwide.

“Our study suggests that mild covid-19 patients are at risk for a small number of health outcomes and most of them are resolved within a year from diagnosis,” say the researchers.

“Importantly, the risk for lingering dyspnoea was reduced in vaccinated patients with breakthrough infection compared with unvaccinated people, while risks of all other outcomes were comparable,” they add.

Prof. Jan Felix Drexler (left) and co-author Dr. Anges Yadouleton (center) in the Laboratory of Viral Hemorrhagic Fever (LFHB) in Benin © Charité | Anna-Lena Sander

First discovered a year ago in South Africa, the SARS-CoV-2 variant later dubbed “Omicron” spread across the globe at incredible speed. It is still unclear exactly how, when and where this virus originated. Now, a study published in the journal Science* by researchers from Charité – Universitätsmedizin Berlin and a network of African institutions shows that Omicron’s predecessors existed on the African continent long before cases were first identified, suggesting that Omicron emerged gradually over several months in different countries across Africa.

Since the beginning of the pandemic, the coronavirus has been constantly changing. The biggest leap seen in the evolution of SARS-CoV-2 to date was observed by researchers a year ago, when a variant was discovered that differed from the genome of the original virus by more than 50 mutations. First detected in a patient in South Africa in mid-November 2021, the variant later named Omicron BA.1 spread to 87 countries around the world within just a few weeks. By the end of December, it had replaced the previously dominant Delta variant worldwide.

Since then, speculations about the origin of this highly transmissible variant have centered around two main theories: Either the coronavirus jumped from a human to an animal where it evolved before infecting a human again as Omicron, or the virus survived in a person with a compromised immune system for a longer period of time and that’s where the mutations occurred. A new analysis of COVID-19 samples collected in Africa before the first detection of Omicron now casts doubt on both these hypotheses.

The analysis was carried out by an international research team led by Prof. Jan Felix Drexler, a scientist at the Institute of Virology at Charité and the German Center for Infection Research (DZIF). Other key partners in the European-African network included Stellenbosch University in South Africa and the Laboratory of Viral Hemorrhagic Fever (LFHB) in Benin. The scientists started by developing a special PCR test to specifically detect the Omicron variant BA.1. They then tested more than 13,000 respiratory samples from COVID-19 patients that had been taken in 22 African countries between mid-2021 and early 2022. In doing so, the research team found viruses with Omicron-specific mutations in 25 people from six different countries who contracted COVID-19 in August and September 2021 – two months before the variant was first detected in South Africa.

To learn more about Omicron’s origins, the researchers also decoded, or “sequenced,” the viral genome of some 670 samples. Such sequencing makes it possible to detect new mutations and identify novel viral lineages. The team discovered several viruses that showed varying degrees of similarity to Omicron, but they were not identical. “Our data show that Omicron had different ancestors that interacted with each other and circulated in Africa, sometimes concurrently, for months,” explains Prof. Drexler. “This suggests that the BA.1 Omicron variant evolved gradually, during which time the virus increasingly adapted to existing human immunity.” In addition, the PCR data led the researchers to conclude that although Omicron did not originate solely in South Africa, it first dominated infection rates there before spreading from south to north across the African continent within only a few weeks.

“This means Omicron’s sudden rise cannot be attributed to a jump from the animal kingdom or the emergence in a single immunocompromised person, although these two scenarios may have also played a role in the evolution of the virus,” says Prof. Drexler. “The fact that Omicron caught us by surprise is instead due to the diagnostic blind spot that exists in large parts of Africa, where presumably only a small fraction of SARS-CoV-2 infections are even recorded. Omicron’s gradual evolution was therefore simply overlooked. So it is important that we now significantly strengthen diagnostic surveillance systems on the African continent and in comparable regions of the Global South, while also facilitating global data sharing. Only good data can prevent policymakers from implementing potentially effective containment measures, such as travel restrictions, at the wrong time, which can end up causing more economic and social harm than good.”

A home test to help patients manage long covid at home has been developed and is available to download.

The adapted Autonomic Profile (aAP) test can be done by anyone with symptoms of autonomic dysfunction in conditions such as long covid, chronic fatigue syndrome, fibromyalgia, and diabetes 1 and 2 where people get feelings such as dizziness or blackouts.

The team behind the test was led by Dr Manoj Sivan, Associate Professor in the University of Leeds’ School of Medicine, and Research Lead for the Leeds Long Covid service. Dr Sivan is Europe’s leading advisor on the treatment of the condition and led the development of the first long COVID measure, called C19-YRS (Yorkshire Rehabilitation Scale), which has been advocated for use by NHS England and NICE.

Autonomic testing is usually done on a single occasion in hospital. Patients lie on a tilt table, and their heart rate and blood pressure are measured as the table is manoeuvered from the horizontal position to vertical.

The new aAP test can be done at home, meaning patients can better understand and self-manage their condition over time, as well as monitor the effectiveness of treatment prescribed by clinicians. It also reduces demand on NHS resources. By recording their blood pressure and heart rate at key times and in response to key activities, patients can work out if foods, exercise or other activities trigger their symptoms, and make lifestyle changes accordingly.

The results can also be shared with clinicians to help them understand how patients’ bodies react to common triggers and stimuli in everyday life.

Joanna Corrado, Clinical Research Fellow in Leeds’ School of Medicine, and part of the research team, said: “Fluctuations in the condition, referred to as crashes, are one of biggest problems long covid patients face. The aAP test allows patients to capture these fluctuations more reliably, in addition to having a one-off test in the hospital. The test enables capturing symptoms in relation to physical activities, mental work, emotional stress and food intake. This allows them to make adjustments to their daily activities and avoid the fluctuations as much as possible. This can be very empowering for patients.”

Autonomic system

The autonomic system regulates involuntary physiologic processes including heart rate, blood pressure, breathing and digestion. Dysfunctions develop when the nerves of this system are damaged, such as after a disease like COVID-19. Symptoms include dizziness and fainting on standing up; an inability to alter heart rate with exercise, or exercise intolerance, and digestive difficulties like loss of appetite, bloating, diarrhoea; palpitations, dizziness, brain fog and sleep problems.

Current tests to evaluate dysfunctions of the autonomic system are based on cardiovascular reflexes triggered by performing activities that stimulate the system. Blood pressure and heart rate can be affected by standing up or lying on a tilt table; breathing techniques; muscle contracting or relaxing, and mental arithmetic.

Development of the aAP began during the COVID-19 pandemic to enable patients to undergo testing and monitoring at home, rather than attend hospital.

It involves patients using a blood pressure monitor and heart rate monitor at home to observe physiological responses to key activities in daily life. Readings are taken on waking, after meals, after exertion and before sleep. The patients record changes in blood pressure and heart rate, and also record their symptoms, such as dizziness, on an aAP diary sheet.

Unlike other standardised tests, there is no need to abstain from caffeine, nicotine, alcohol or medications for the aAP, as the purpose is for patients to test in their daily life the reaction to common  stimuli, and record normal or abnormal autonomic responses.

Dr Sivan said: “There are 2 million individuals with long covid in the UK and it is estimated more than a third of them might have altered functioning of the autonomic nervous system. This can present not only as feeling dizzy or racing of the heart but also as fatigue, exercise intolerance, brain fog, pain, bowel and bladder symptoms. This test gives people with long covid easy access to diagnosis and monitor their own symptoms at home, and gives them reliable evidence of the situations that trigger their symptoms.”