Long COVID: Systemic inflammation may persist months after infection

Patients who had been infected with COVID-19 continue to experience symptoms at medium-term follow-up, showing greater high-sensitivity C-reactive protein (hsCRP) than controls, results of a study have shown.

“Higher hsCRP … and the positive association of hsCRP with time suggest ongoing systemic inflammation in patients persisting for months after COVID-19,” the researchers said.

In this case-control study, researchers interviewed 174 patients with virologically proven COVID-19 and 75 age- and gender-matched controls (mean age 46.1 years) to examine symptoms and health-related quality of life. They also carried out biochemical tests.

Demographics data between COVID-19 patients and controls were similar. Over a median follow-up of 173.5 days, more post-COVID-19 patients experienced shortness of breath, fatigue, arthralgia, abnormal taste of food (p<0.001), and anosmia than did controls. [Am J Med 2025;138:131-139]

In addition, patients had worse scores in the general health and role physical domains of the Short Form Survey-36 (SF-36) questionnaire, as well as significantly higher hsCRP. A positive association was also observed between hsCRP and time.

Factors significantly predictive of shortness of breath included age, female gender, and white cell count, troponin I, and lower haemoglobin levels at follow-up.

Further investigations are warranted to explore the role troponin play, along with markers of inflammation and endothelial dysfunction at long-term follow-up, according to the investigators.

Long COVID

“Our data show that, compared with controls, post-COVID-19 patients had persistent symptoms after a medium follow-up of 173.5 days. These included shortness of breath, anosmia, loss of taste, fatigue, arthralgia, and a perception of deterioration in general condition,” the researchers said.

These findings are consistent with those of a study by Huang and colleagues, who reported 63 percent of patients with fatigue or muscle weakness 6 months after COVID-19. Likewise, the closely related SARS and MERS have also caused similar long-term symptoms. [J Rehabil Med 2020;52:jrm00063; J Psychiatr Res 2021;137:1-6; Arch Intern Med 2009;169:2142-2147]

“In our study, [COVID-19 patients] also exhibited worse scores when considering both general health and role physical scores on the SF-36 questionnaire,” the researchers said.

This study was carried out before the implementation of vaccination and did not assess the impact of the virus in the postvaccination era.

“However, one has to appreciate that, although the advent of effective immunization has markedly changed the natural history of COVID-19, immunization rates in many regions of the world remain low,” the researchers said.

By 7 March 2023, only 65.0 percent of the global population had received full vaccination against COVID-19. In low-income countries, the rate was only 24.9 percent. Even in countries with a high vaccination rate, many individuals contracted COVID-19 prior to the availability of immunization. [https://data.who.int/dashboards/covid19/cases?n=c]