Comparison of post-COVID-19 symptoms two years after infection with SARS-CoV-2

In a recent study published in JAMA Network is openresearchers compared the presence of post-coronavirus 2019 (COVID-19) symptoms between hospitalized and non-hospitalized patients in Spain.

Study: Post-COVID-19 symptoms 2 years after SARS-CoV-2 infection among hospitalized versus non-hospitalized patients.  Image credit: TZIDO SUN / Shutterstock
Stady: Post-COVID-19 symptoms 2 years after SARS-CoV-2 infection among hospitalized versus non-hospitalized patients. Image credit: TZIDO SUN / Shutterstock

In addition, the researchers identified potential risk factors associated with developing postmenopausal womenSymptoms of COVID-19 disease 2 years after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.


Many countries are optimistic that the COVID-19 pandemic is becoming endemic. However, the occurrence or persistence of symptoms after the acute phase of SARS-CoV-2 infection, colloquially called “long COVID,” is the new pressing issue that requires the attention of researchers and governments alike.

Studies have reported more than 100 post-COVID-19 symptoms affecting multiple human organs (eg, cardiovascular, nervous, respiratory, and musculoskeletal). Several reviews have shown that people who have experienced post-COVID-19 symptoms have worsened health-related quality of life.

Although there is no shortage of studies and meta-analyses evaluating the prevalence of post-COVID-19 symptoms, most have collected data from hospitalized and non-hospitalized patients. And their follow-up periods were consistently less than six months.

Recently, some meta-analyses directly compared hospitalized versus non-hospitalized patients with a follow-up period of up to six months after acute infection. Comparative data with follow-up periods greater than 1 year after acute SARS-CoV-2 infection are still not available.

about studying

In this study, the researchers recruited patients hospitalized with COVID-19 from two urban hospitals in Spain and another group of patients hospitalized with SARS-CoV-2 from an external setting managed by their general practitioners. They used Microsoft randomization software to select 400 patients for each study group. The current cross-sectional study followed the Guidelines for Strengthening Reporting of Observational Studies in Epidemiology (STROBE). All study participants contracted SARS-CoV-2 infection during the first wave of the COVID-19 pandemic between March 20 and April 30, 2020. It should be noted that they did not experience penetrating infection by other variants of SARS-CoV-2.

The team verified SARS-CoV-2 infection in these individuals through reverse transcription-polymerase chain reaction (RT-PCR) test results of nasal or oral swab samples. They used medical records to confirm their demographic (age and gender), clinical, and hospitalization data. Furthermore, they scheduled a telephone interview by trained researchers for all participants who agreed to follow-up two years after acute injury. At the interview, they inquired about symptoms that appear after hospitalization or the stage of acute infection. Also, make sure whether or not these symptoms persist for the duration of the study.

The researchers considered symptoms attributed to COVID-19 only and with onset no later than a month after infection with SARS-CoV-2. The team systematically assessed several post-COVID-19 symptoms during the study. Examples include shortness of breath, fatigue, loss of smell, pain symptoms, and brain fog. However, they allowed all participants to report any other symptoms they experienced that they considered relevant.

The researchers tracked evidence of the emotional and societal impact of the COVID-19 pandemic. So they used the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI) for anxiety and depression symptoms, and sleep quality ratings, respectively. For HADS-A and HADS-D, a cut-off score of 12 or 10 points or greater indicated anxiety and depressive symptoms, respectively. Similarly, for the PSQI, a cutoff of 8 points or more was considered an indicator of poor sleep quality.

Finally, the researchers presented the data as averages or percentages. They calculated adjusted odds ratios with 95% confidence intervals. For the primary outcome, they compared the differences in post-COVID-19 symptoms between the two study groups using the χ2 test or one-way analysis of variance tests. Furthermore, they used multivariate logistic regression to determine the possible association of post-COVID-19 symptoms with variables identified in the acute phase, which adjusted for covariates in the two study groups separately.


According to the authors, this study is the largest follow-up comparison between inpatients and outpatients. Its results showed that at least one post-COVID-19 symptom was present in 59.7% and 67.5% of hospitalized and non-hospitalized patients, respectively, two years after infection with SARS-CoV-2. Another study by Huang et al. It also showed that 55% of hospitalized patients showed post-COVID-19 symptoms two years after discharge. However, there is no other study to directly compare the data of this study to non-hospitalized patients.

The researchers noted that shortness of breath and loss of smell were the symptoms associated with COVID-19 most prevalent initially among hospitalized and non-hospitalized patients, respectively. While the former is an alarming symptom that occurs during severe illness, the latter sets COVID-19 apart from the clinical manifestations of other respiratory infections. Also, people with anosmia often do not seek hospitalization.

Fatigue, like musculoskeletal pain, is the most prevalent symptom in the first year after infection with SARS-CoV-2, proving its association with a higher post-COVID-19 burden. Studies suggest that fatigue after COVID-19 shares features of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). Exponential recovery curve analysis revealed that shortness of breath decreased in the years following COVID-19. Interestingly, however, fatigue did not decrease but persisted 2 years after COVID-19, indicating that it is the most prevalent and long-lasting post-COVID-19 symptom.

Asteri study et al. suggested that female gender and the number of symptoms of COVID-19 onset at hospital admission, but not disease severity were potential risk factors for prolonged COVID. The researchers did not identify these risk factors in the hospital cohort of this study because pre-existing medical comorbidities were the only variable associated with post-COVID-19 fatigue and shortness of breath. Instead, they noted that the number of symptoms in the acute phase was a risk factor for post-COVID-19 fatigue among out-of-hospital patients. A possible explanation could be that those with severe infections had a higher viral load, which is associated with a stronger immune response, which in turn facilitated the prolonged development of COVID.

Patients in both study groups did not display symptoms of anxiety and depression, as evidenced by the mean HADS-A and HADS-D scores.


Overall, the results of the current study indicated slight differences in the onset of COVID-19 and post-COVID-19 symptoms between in-hospital and non-hospital COVID-19 survivors, reintroducing the notion that there is no association between prolonged COVID development and COVID-19 severity during the first phase. acute infection.

Because the observed rates of post-COVID-19 symptoms were comparable between hospitalized and non-resident patients, it is critical to monitor and treat for prolonged COVID in all patients who develop COVID-19.

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