Symptomatic Trends and Time to Recovery for Long COVID Patients Infected During the Omicron Phase, 2025, Akiyama et al.

[SNT Gatchaman]

Symptomatic Trends and Time to Recovery for Long COVID Patients Infected During the Omicron Phase

Spoiler: Authors

Akiyama, Hiroshi; Sakurada, Yasue; Honda, Hiroyuki; Matsuda, Yui; Otsuka, Yuki; Tokumasu, Kazuki; Nakano, Yasuhiro; Takase, Ryosuke; Omura, Daisuke; Ueda, Keigo; Otsuka, Fumio

BACKGROUND
Since the pathophysiology of long COVID is not yet fully understood, there are no specific methods for its treatment; however, its individual symptoms can currently be treated. Long COVID is characterized by symptoms that persist at least 2 to 3 months after contracting COVID-19, although it is difficult to predict how long such symptoms may persist.

METHODS
In the present study, 774 patients who first visited our outpatient clinic during the Omicron period from February 2022 to October 2024 were divided into two groups: the early recovery (ER) group (370 cases; 47.8%), who recovered in less than 180 days (median 33 days), and the persistent-symptom (PS) group (404 cases; 52.2%), who had symptoms that persisted for more than 180 days (median 437 days). The differences in clinical characteristics between these two groups were evaluated.

RESULTS
Although the median age of the two groups did not significantly differ (40 and 42 in ER and PS groups, respectively), the ratio of female patients was significantly higher in the PS group than the ER group (59.4% vs. 47.3%). There were no significant differences between the two groups in terms of the period after infection, habits, BMI, severity of COVID-19, and vaccination history. Notably, at the first visit, female patients in the PS group had a significantly higher rate of complaints of fatigue, insomnia, memory disturbance, and paresthesia, while male patients in the PS group showed significantly higher rates of fatigue and headache complaints. Patients with more than three symptoms at the first visit were predominant in the PS groups in both genders. Notably, one to two symptoms were predominant in the male ER group, while two to three symptoms were mostly reported in the female PS group. Moreover, the patients in the PS group had significantly higher scores for physical and mental fatigue and for depressive symptoms.

CONCLUSIONS
Collectively, these results suggest that long-lasting long COVID is related to the number of symptoms and presents gender-dependent differences.

Web | PDF | Journal of Clinical Medicine | Open Access

 

[Hutan]

A Japanese study - Okayama.

Interesting to see another study mentioning, in it's first sentence, that Covid-19 was first reported in Wuhan, China . That fact has zero relevance to the study. I'm idly wondering why this is happening - is it seen as politically useful?

The pathophysiology of long COVID remains complex, involving microthrombus, inflammation, autoimmunity, viral persistence, neurological damage, and vascular dys-function [4,5]. This complexity suggests the need for multidisciplinary rather than single therapeutic approaches [6]. Long COVID varies not only in terms of symptoms but also in severity, as some people have mild symptoms while others present symptoms so severe that they interfere with their daily life and employment [7]. The prolongation of poor physical and mental conditions not only reduces an individual’s quality of life (QOL), but also poses serious public health challenges such as an increased burden on the health care system and withdrawal from the labor force.

These papers from countries that we don't hear much from in terms of reports from people with Long Covid themselves provide some news of how Long Covid is being seen. It looks as though Long Covid is being simultaneously seen as a single thing, but also involving a wide range of pathophysiologies, which seem to have moved beyond speculative theories to fact. Still, there is no suggestion in that description of psychosomaticism. There is a recognition that the problem 'poses serious public health challenges' including withdrawal from the labour force.

I thought this was a decent statement of Long Covid prevalence:

The reported prevalence of long COVID varies significantly, depending on the study design, target population, and timing of assessment. Approximately 10 to 30% of infected individuals experience persistent symptoms lasting beyond one to three months after infection [8–11]. The related symptoms can persist for weeks, months, or even longer; global estimates for 2022 indicate that approximately 15% of individuals will still have symptoms at 12 months [12]. In a matched cohort study conducted in Berlin, Germany, most recovered COVID-19 patients regained their health within 6.5 months. On the other hand, symptoms such as taste and smell disturbances, as well as neurological and cognitive impairments (e.g., so-called “brain fog”), require a longer recovery period [13,14].

Good that they recognise the overlap with ME/CFS, and interesting to see them draw a line at 180 days between recovery and chronic illness.

Notably, recent studies have suggested a significant clinical overlap between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), particularly in symptoms such as post-exertional malaise, fatigue, and cognitive impairment [18]. Furthermore, SARS-CoV-2 has been hypothesized as a potential trigger for ME/CFS [19–21]. Based on this similarity, we considered the 180-day point to be a clinically meaningful threshold for distinguishing between recovery and progression to chronic illness in long COVID.

 

[Hutan]

Medical records were analyzed during the data extraction period from 1 May 2025 to 22 May 2025. The duration of outpatient follow-up was calculated based on the initial and final consultation dates recorded in the medical records. Patients were classified into two groups according to their follow-up duration: those with a follow-up period of less than 180 days were categorized into the early recovery (ER) group, whereas those with a follow-up period of 180 days or more were classified into the persistent-symptom (PS) group.

I think the method of classifying patients into the early recovery (ER) group and persistent-symptom (PS) group may have some bias, given it requires the person to stick with the clinic and come to outpatient consultations. Some people with persisting symptoms may give up if they aren't getting any useful treatment. Possibly, men may be less inclined to keep turning up to appointments that aren't helping.

Comparative analyses between the ER and PS groups were conducted to evaluate the initial consultation age, gender, presenting symptoms, BMI, history of alcohol consumption, smoking status, vaccination history, severity of COVID-19 in the acute phase [22], laboratory test results, and questionnaire scores from the FAS [23,24], EQ-5D-5L [25], and SDS [26].

Laboratory data for hemoglobin (Hb), inflammatory markers (C-reactive protein: CRP and ferritin), liver functions (albumin: Alb, aspartate aminotransferase: AST, alanine aminotransferase: ALT), renal functions (creatinine: CRE), and low-density lipoprotein cholesterol (LDL-C) were obtained from medical records and analyzed in this study. Laboratory information on the following endocrine parameters was also obtained: adrenocorticotropin (ACTH), cortisol, free thy-roxin (FT4), and thyrotropin (TSH).

774 patients, all assessed as having had an Omicron Covid-19 infection.

 

[Hutan]

I think this is quite an interesting study. Very few of the patients had had a severe ME/CFS infection, so the findings are not complicated by overt tissue damage or treatments given for severe disease.

Figure 1 gives a nice chart of a diminishing numbers of patients having their final consultation over time. There is a steep decrease and then a long tail. The issues around reasons why a person might stop attending the clinic is a bit of a confounder though. I'd like to see more versions of this chart made with data that is a bit more robust.

However, a significant difference was observed in the gender distribution, with female patients comprising a higher proportion in the PS group than the ER group (59.4% vs. 47.3%, ** p < 0.01).

So, nearly 60% of people in the persisting symptoms group were women, and only 47% of people in the early recovery were women. 60% isn't a huge female:male skew. As I noted, the willingness to keep turning up to appointments when no real assistance is being provided might account for part of that skew, given what we know about average differences in a willingness to see a doctor in males and females.

Of the 774 patients in the study, 415 of them were female. So, there was a slight female skew in those attending the first appointment (54%).


No differences in:

smoking, alcohol
BMI
severity of initial disease
vaccination status
lab tests: haemoglobin, cortisol, ACTH, liver function, CRP, ferritin, TSH, FT4,

Worse status for the persisting symptoms group in:
quality of life and depression at initial visit - not surprising given the overlap in "depression" symptoms and higher symptom load
more likely to report multiple symptoms at initial visit
higher LDL-cholesterol levels in males, also slightly elevated in female




Symptoms - interesting to see how prevalent "fatigue" is, dwarfing all the other symptoms.