General characteristics

The study evaluated a total of 130 patients surviving COVID-19 pneumonia. The group with post COVID-19 pulmonary sequelae consisted of 17 males (63%) and 10 females (37%); with a mean (standard deviation) age of 65.3 (9.9) years. Secondly, the group without sequelae consisted of 46 males (44.7%) and 57 females (55.3%); with a mean (standard deviation) age of 53.4 (16.2) years. Table 1 shows the demographic characteristics, comorbidities, and symptoms at 3 months. Age, Charlson index, chest X-ray score and spirometric values are shown in Table 2.

Table 1 Qualitative characteristics of the included patients.
Table 2 Quantitative characteristics of included patients.

The predominant symptoms in both groups were dyspnea, asthenia and anosmia- ageusia. Spirometry was normal in both groups. We found significant differences between the two groups in age and in the Charlson index, with older age and more comorbidity in the group with pulmonary sequelae. In addition, we also found differences in hospital stay and in the extent of pneumonia, having stayed more days hospitalized and with a higher score in the group with sequelae.

Patients with pulmonary sequelae underwent additional studies with pulmonary diffusion and thoracic HRCT. Lung diffusion was normal with a mean DLCO of 79.50% (18.14) and range 55.0–108.0. Both spirometry and lung diffusion were redetermined at 12 months with the following results: mean FVC of 3690 ml (1013.0) and range 1430.0–5140.0, mean FVC% of 106.5% (14.3) and range 64.0–136.0, mean FEV1 of 2852.3 (766.9) and range 1190.0–4300.0, mean FEV1% of 105.6% (14.4%) and range 70.0–135.0, mean FEV1%FVC of 76.7% (7.8) and range 57.0–91.0 and mean DLCO% of 84.8 (14.4) and range 55.0–112.0. No significant differences were found in lung function tests at 3 and 12 months: FVC (p = 0.423), FVC% (p = 0.087), FEV1 (p = 0.233), FEV1% (p = 0.130), FEV1%FVC (p = 0.527), DLCO% (0.296).

The most frequently observed radiological findings in patients with alterations in CT were GGO, present in 88.9% of cases. However, the extension of the GGO was minimal or slight in most of the participants (55.5%). The peripheral distribution and in the middle and lower areas were the predominant locations. Reticulation (77.7%), fine parenchymal bands (63.0%), mosaic (40.7%) and distortion with traction bronchiectasis (29.6%) were the other alterations observed, but with minimal or slight extension. Severe radiological alterations were detected in 14.8% of the cases.

Analysis of evolution and differences in HRQoL between patients with Post COVID-19 pulmonary sequelae and patients without post COVID-19 pulmonary sequelae

A general linear repeated measures model with the within-subject factor "Time" (Time 1: 3 months post infection and Time 2: 12 months post infection)" and the between-subject factor "Group" (patients with post infection sequelae and patients without post infection sequelae) was performed to analyse the evolution in the different dimensions of HRQoL, as well as possible differences according to group.

Regarding the variable Time, no differences were found between Time 1 (3 months post infection) and Time 2 (12 months post infection) in any of the HRQoL dimensions (p > 0.05), except in the case of the PCS dimension F(1,128) = 7.045, p = 0.009, n2partial = . 052 and MCS F(1,128) = 5.615, p = 0.019, n2partial = 0.042. In the case of PCS, at Time 2 participants obtained lower scores compared to Time 1; however, with respect to MCS, at Time 2 participants showed higher scores compared to Time 1.

Regarding the interaction "Time × Group", no significant interaction effect was found in most dimensions, except for GH F(1,128) = 8.761, p = 0.004, n2partial = 0.064. However, post-hoc analysis did not reveal significant differences in any specific time (p > 0.05).

Finally, no significant main effect of the factor "Group" was found (p > 0.05).

Table 3 shows the means and standard deviations of the scores obtained in each of the HRQoL dimensions both in the total sample and in each of the groups separately, taking into account the assessment time.

Table 3 Differences in the scores of the items of the SF-36 questionnaire at 3 and 12 months after infection.

Analysis of evolution and differences in HRQoL between patients with post COVID-19 pulmonary sequelae and patients without post COVID-19 pulmonary sequelae controlling for possible confounders

Considering that several differences have been identified in the characteristics of the sample at baseline, mainly regarding age, Charlson index, days of hospitalization and Pneumonia extension at initial radiograph; analyses of repeated measures were replicated but including these variables as covariates in the model.

In relation to the interaction "Time × Group", the significant effect of the interaction was maintained in the dimension GH F(1,124) = 6.313, p = 0.013, n2partial = 0.048. No significant effect of this interaction was found in any other dimension of HRQoL (p > 0.05).

Regarding the effect of the main factor "Group", differences were found in the dimension VT F(1,124) = 4.223, p = 0.042, n2partial = 0.033. For the remaining HRQoL dimensions, no significant main effect of the Group factor was found.

In relation to the covariates, days of hospitalization emerged significant in the between-subject effects in the following dimensions: FP F(1,124) = 4.453, p = 0.037, n2partial = 0.035; RP F(1,124) = 7.070, p = 0.009, n2partial = 0.054; PA F(1,124) = 6.435, p = 0.012, n2partial = 0.049; VT F(1,124) = 4.330, p = 0.039, n2partial = 0.034; SF F(1,124) = 6.137, p = 0.015, n2partial = 0.047; RE F(1,124) = 4.482, p = 0.036, n2partial = 0.035; MH F(1,124) = 4.548, p = 0.035, n2partial = 0.035; PCS F(1,124) = 4.022, p = 0.047, n2partial = 0.031 and MCS F(1,124) = 4.518, p = 0.036, n2partial = 0.035.

Charslon’s index was significant for between-subject effects in GH F(1,124) = 5.160, p = 0.025, n2partial = 0.040 and SF F(1,124) = 4.411, p = 0.038, n2partial = 0.034. In addition, it was significant for within-subject effects in the case of MH F(1,124) = 4.850, p = 0.029, n2partial = 0.038.

Radiological score at baseline was significant in between-subject effects in TV F(1,124) = 4.478, p = 0.036, n2partial = 0.035 and in MH F(1,124) = 4.662, p = 0.033, n2partial = 0.036.

Institutional review board statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Investigación de Medicamentos del departamento de salud de Alicante (Dictamen Favorable PI2021-090 (ISABIAL 2021-0145)).

Informed consent

Consent was obtained from all subjects involved in the study.

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