A new analysis of research conducted during the first two years of the pandemic helps crystallise some answers that have been emerging, finding that patients over 40, those with previous health issues and those who had a severe coronavirus infection, had more risk of developing long Covid. And it affirmed a growing consensus that vaccination lowers that risk.
The analysis, by a team of researchers in Britain and published in the journal JAMA Internal Medicine, looked at 41 studies published between the beginning of the pandemic and 5 December 2022, involving 860 783 patients.
The report evaluated the patients’ risk of post-Covid symptoms – including shortness of breath, fatigue, brain fog, headache, and loss of taste and smell – more than three months after their infection, reports The New York Times.
People who received two doses of a Covid vaccine before becoming infected were 43% less likely to develop long Covid. The analysis did not look at the role of boosters.
Maternal mortality
Government data show that death of pregnant women in 2021 increased by 40% compared with 2020 and by 60% compared with 2019. Covid was a contributing factor in the rise, a separate report suggests.
The authors wrote that the emerging evidence suggested that vaccination reduced the risk of long-term symptoms “even in individuals with other risk factors, such as older age or high BMI”.
Other studies that were not included in the analysis have also suggested that vaccines can reduce, though not eliminate, the risk of long Covid.
Risk factors analysed in the paper included:
Being female
Women were one and a half times as likely as men to develop long Covid. The authors and other researchers have suggested several possible reasons for this, including that hormone levels or disruption in hormone production may perpetuate inflammation caused by the initial infection and that higher levels of some antibodies in women might contribute to lingering symptoms.
Being over 40
The long Covid patients in the analysis were about 20% more likely to be older than 40. The analysis found that people 70 and older had the same risk as those who were 40 to 69, but the researchers suggested that might be because people over 70 were more likely to die from their initial infection.
Being obese
People were at increased risk for long Covid if they were obese, the analysis found. Obesity, they wrote, often involves a metabolic inflammatory process that could prolong post-Covid health issues.
Being a smoker
Smoking was also a risk factor, the researchers found, although they said it was unclear if that was because of the smoking itself or illnesses associated with smoking.
Having previous medical conditions
Of the medical issues analysed in the study, immunosuppressive conditions appeared to lead to the greatest increased risk of long Covid. People with chronic obstructive pulmonary disease, ischaemic heart disease or asthma faced the next highest levels of increased risk. There was also elevated risk of long Covid for people with anxiety, depression, chronic kidney disease or diabetes.
The sicker people were during their initial infection, the more likely they were to experience lingering health problems. Patients who were hospitalised, whether in intensive care or not, were nearly two and a half times as likely to develop long Covid than patients who were not hospitalised, the analysis found.
“Patients with previous critical illness represent a high-risk population, and their follow-up should reflect intensive plans for prevention, rehabilitation and treatment of the ongoing debilitating symptoms,” the authors wrote.
However, since a majority of people infected with the coronavirus have not needed to be hospitalised, there are greater numbers of long Covid patients whose initial infection was relatively mild.
Other research, not included in the analysis, has focused on more detailed biological characteristics. One study published in 2022 found that people were more likely to develop long Covid if, at the time of their infection, they had factors including certain autoantibodies – antibodies that mistakenly attack tissues in the body as they do in conditions like lupus and rheumatoid arthritis – or reactivated Epstein-Barr virus, a virus that infects most people and then usually becomes dormant.
The new analysis involved patients infected during waves of various coronavirus variants, but the authors did not analyse the variants separately.
It is unlikely that the risk factors associated with long Covid would change with new variants, they wrote.
Study details
Risk Factors Associated With Post−COVID-19 ConditionA Systematic Review and Meta-analysis
Vasiliki Tsampasian, Hussein Elghazaly, Rahul Chattopadhyay, et al.
Published in JAMA Internal Medicine on 23 March 2023
Key Points
Question Which individuals are at risk of developing post−COVID-19 condition (PCC)?
Findings This systematic review and meta-analysis of 41 studies including 860 783 patients found that female sex, older age, higher body mass index, smoking, preexisting comorbidities, and previous hospitalisation or ICU admission were risk factors significantly associated with developing PCC, and that SARS-CoV-2 vaccination with 2 doses was associated with lower risk of PCC.
Meanings The findings of this systematic review and meta-analysis provide a profile of the characteristics associated with increased risk of developing PCC and suggest that vaccination may be protective against PCC.
Abstract
Importance
Post−Covid-19 condition (PCC) is a complex heterogeneous disorder that has affected the lives of millions of people globally. Identification of potential risk factors to better understand who is at risk of developing PCC is important because it would allow for early and appropriate clinical support.
Objective
To evaluate the demographic characteristics and comorbidities that have been found to be associated with an increased risk of developing PCC.
Study selection
The meta-analysis included all published studies that investigated the risk factors and/or predictors of PCC in adult (≥18 years) patients.
Data Extraction and Synthesis
Odds ratios (ORs) for each risk factor were pooled from the selected studies. For each potential risk factor, the random-effects model was used to compare the risk of developing PCC between individuals with and without the risk factor. Data analyses were performed from December 5, 2022, to February 10, 2023.
Main Outcomes and Measures
The risk factors for PCC included patient age; sex; body mass index, calculated as weight in kilograms divided by height in meters squared; smoking status; comorbidities, including anxiety and/or depression, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, immunosuppression, and ischaemic heart disease; previous hospitalisation or ICU (intensive care unit) admission with COVID-19; and previous vaccination against COVID-19.
Results
The initial search yielded 5334 records of which 255 articles underwent full-text evaluation, which identified 41 articles and a total of 860 783 patients that were included. The findings of the meta-analysis showed that female sex (OR, 1.56; 95% CI, 1.41-1.73), age (OR, 1.21; 95% CI, 1.11-1.33), high BMI (OR, 1.15; 95% CI, 1.08-1.23), and smoking (OR, 1.10; 95% CI, 1.07-1.13) were associated with an increased risk of developing PCC. In addition, the presence of comorbidities and previous hospitalisation or ICU admission were found to be associated with high risk of PCC (OR, 2.48; 95% CI, 1.97-3.13 and OR, 2.37; 95% CI, 2.18-2.56, respectively). Patients who had been vaccinated against COVID-19 with 2 doses had a significantly lower risk of developing PCC compared with patients who were not vaccinated (OR, 0.57; 95% CI, 0.43-0.76).
Conclusions and Relevance
This systematic review and meta-analysis demonstrated that certain demographic characteristics (eg, age and sex), comorbidities, and severe COVID-19 were associated with an increased risk of PCC, whereas vaccination had a protective role against developing PCC sequelae. These findings may enable a better understanding of who may develop PCC and provide additional evidence for the benefits of vaccination.
See more from MedicalBrief archives:
Impaired lung function in 25% of long Covid patients – Dutch study
Most long Covid symptoms go after a year – large Israeli cohort study
More than half of patients suffer long Covid symptoms – SA study
WHO estimates 17m long COVID cases in Europe and urges action