Self-reported long COVID symptoms not identified in diagnostic tests

The rapid transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections and approximately seven million deaths from coronavirus disease 2019 (COVID-19) worldwide. The vast amount of research dedicated to understanding COVID-19 has demonstrated that this infection is often accompanied by clinical features related to other organs than the lungs.

These symptoms and signs often persist for weeks or months after acute illness has resolved, which is a condition now referred to as ‘long COVID.’ A recent study in Nature Communications Medicine describes chronic symptoms related to physical or mental functioning following SARS-CoV-2 infection.

Study: Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study. Image Credit: Agenturfotografin / Shutterstock.com

Introduction

Most COVID-19 survivors recover within one year, even after severe disease. However, many patients with mild-to-moderate COVID-19 reported prolonged symptoms ranging from fatigue, brain fog, and breathlessness, as well as many others.

Long COVID is estimated to affect up to half of all people with a history of non-severe COVID-19; however, the actual prevalence has not been established.

The current study included over 1,700 adults with a test-confirmed history of SARS-CoV-2 positivity in Iceland who were infected before October 2020. The period from the infection to participating in the study was about eight months.

Individuals with a history of COVID-19 were confirmed to have had the infection by the presence of anti-nucleoprotein (anti-N) antibodies. The researchers asked these individuals about their symptoms to compare them with those of controls.

Both historical and contemporary controls were used. The latter group had tested negative for SARS-CoV-2, while historical controls were those who had participated in the study before the pandemic began.

What did the study show?

Of the almost 90 symptoms in the questionnaire, over 40 were associated with prior infection. Conversely, objective changes occurred in very few of the over 150 tests of physical and cognitive parameters or blood composition.

About 5% of cases reported experiencing severe symptoms six months following infection; however, only 1% reported persistent symptoms at 13 months. About 25% of all patients sought medical help with their chronic symptoms.

Based on the questionnaire, the most commonly disrupted functions were those of smell, taste, memory ,and dyspnea. Taste disturbance and smell alterations were 10 and 12 times more common in cases than controls, respectively. Shortness of breath and memory loss were both three times more common.

Controls rarely reported disturbances of taste or smell at less than 5%, whereas memory loss and dyspnea were reported in about 25% of controls. Alterations in smell and taste were highly correlated, but less so with other symptoms. Overall, several symptoms correlated with each other including shortness of breath, tiredness, weakness, disturbances in memory, and poor concentration.

For seven symptoms, a temporal trend was observed with improved smell and taste over time but more exertion-related tiredness. Most symptoms, except for skin rash, that were associated with SARS-CoV-2 were also more common with severe COVID-19.

Mental health did not show an association with prior SARS-CoV-2 infection. Stress symptoms were decreased among cases as compared to controls, with a reduction in both groups during the pandemic.

The incidence of anxiety and depression remained unchanged following SARS-CoV-2 infection. Life satisfaction, anxiety overall or related to health, depression, and fatigue scores were comparable between both groups. Among cases, more severe symptoms were reported among those with severe infection.

In contrast to the reported symptoms, actual testing showed a less severe impact. Objective tests of memory and neurological function showed that individuals with a history of SARS-CoV-2 infection exhibited decline in a limited number of areas in both fields.

Cases reported reduced smell and taste perception as compared to controls. Hyposmia, selective anosmia for a single or few odors, and selective ageusia were more common among cases. These individuals were less capable of identifying specific odors and found them less pleasant than controls.

Reduced smell perception declined after infection in a small subset of cases with relevant data. While hyposmia improved with time, selective anosmia or ageusia persisted among cases.

Cases also exhibited weaker grip and an 80% increased likelihood of impaired delayed memory recall as compared to controls. All three measures that varied significantly in cases as compared to controls were associated with more severe prior infection.

Other testing results did not show significant differences between cases and controls. These included cardiovascular parameters of heart rate, blood pressure, postural tachycardia, and exercise tolerance, as well as oxygen saturation, markers of inflammation, and markers of liver or kidney function. Additionally, hearing loss was not more frequent in this group as compared to controls.

Mean body weight was not different between cases and controls. In contrast, increased fat mass, lower exercise capacity, lower ‘good’ cholesterol, and higher ‘bad’ cholesterol were related to more severe prior infection. These are known risk factors for severe COVID-19; therefore, the directionality of this association is unknown.

Overall, long COVID affected about 7% of the study cohort, with the median point of evaluation being eight months following infection. Cases were twice as likely to experience long COVID features than controls. When adjusted for other medical conditions, the odds for long COVID among cases increased three-fold that for controls.

Women were more likely to have long COVID, as well as those with a history of severe infection or medical conditions such as immunocompromised states, heart failure, and coronary artery disease.

What are the implications?

The researchers found evidence supporting the occurrence of multiple symptoms several months after recovery from COVID-19. However, their objective testing failed to show differences in actual physical function or cognitive function in post-infection cases as compared to controls.

The small yet significant reduction in grip strength could be due to loss of physical condition following acute COVID-19. This symptom is a recognized and reliable marker for cardiovascular disease and death, which corroborates with an apparent increase in risk for cardiovascular events following acute COVID-19.

Conversely, no objective signs could be found in cardiac biomarkers, thus ruling out chronic myocardial inflammation in COVID-19 survivors. Similarly, inflammatory biomarkers, as well as those used to diagnose hepatic or renal dysfunction, were not raised among cases.

Although cases reported that their hearing had worsened after the pandemic four times more frequently than controls, this could not be confirmed using hearing tests. Similarly, cases reported weight gain after the pandemic more often than controls; however, this was not reflected in body mass index (BMI) values. Memory impairment was also described 3.5 times more often by cases; however, measurements showed an increase by less than 1.8 times.

These observations support an element of response bias in self-reported symptoms following SARS-CoV-2 infection.”

Long COVID may not directly contribute to the symptoms reported by individuals with a history of acute infection, which complicates research into and clinical management of this condition.  

Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.”

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.