Ultimately, 41 patients with aPAP who had a PAP-related condition assessment within the last 1 year completed the questionnaire and telephone follow-up. Two patients were not infected with COVID-19, and the remaining 39 aPAP patients were infected with COVID-19 (Fig. 1). A total of 39 aPAP patients were included in this study. Twelve of the 39 patients (30.77%) had a decrease in oxygen saturation after COVID-19 infection.
Flow diagram of the study cohort. aPAP Autoimmune pulmonary alveolar proteinosis
Baseline demographic information
The mean age of the 39 aPAP patients infected with COVID-19 was 42.56 (± 12.28) years; 25 out of 39 (64.1%) of them were male. Only 2 patients (5.1%) were diagnosed with PAP by Video-assisted Thoracoscopic Surgery (VATS), 14 out of 39 (35.9%) by BALF only, 4 out of 39 (10.3%) by TBLB only, and 19 out of 39 (48.7%) by both BALF and TBLB. All patients were positive for serum GM-CSF antibody test (> 4 μg/ml) with a median of 31.68 (19.31, 70.34) μg/ml. Nine out of 39 patients (23.1%) were ex-smokers and 8 out of 39 patients (20.5%) were current smokers. Eight out of 39 patients (20.5%) had been treated with whole lung lavage, 17 out of 39 (43.6%) had been treated with GM-CSF inhalation that is Molgramostim, and 10 out of 39 (25.6%) had oxygen therapy. Regarding the status of vaccination against the COVID-19, 11 out of 39 patients (28.2%) had never received the vaccine, 5 out of 39 (12.8%) had received 2 doses of the vaccine, and 23 out of 39 (59.0%) had received 3 doses of the vaccine (Table 1).
We compared the 2 groups of patients with or without decreased oxygen saturation after COVID-19 infection and showed that patients who had previous oxygen therapy (decreased oxygen saturation vs. non decreased oxygen saturation: 6/12 vs. 4/27, P = 0.043) were more likely to have oxygen desaturation after COVID-19 infection. Patient age, gender, BMI, history of smoking, history of tuberculosis, comorbidities, history of whole lung lavage and GM-CSF inhalation therapy had no significant difference on whether patients had a decrease in oxygen saturation after COVID-19 infection. In addition, there was no significant difference in the number of doses of vaccination on whether oxygen saturation decreased after COVID-19 infection (P = 0.690) (Table 1).
Effect of baseline laboratory test information on whether oxygen saturation decreased after infection with COVID-19
For baseline ABG, patients with lower baseline PaO2 were more likely to have decreased oxygen saturation after COVID-19 infection. PaO2 (decreased oxygen saturation vs. non decreased oxygen saturation): 74.50 ± 13.61 mmHg versus 86.49 ± 11.92 mmHg, P = 0.009. For other blood parameters, we also found that patients with higher baseline LDH levels were more likely to have decreased oxygen saturation. LDH (decreased oxygen saturation vs. non decreased oxygen saturation): 298 (234, 377) U/L versus 218 (197, 309) U/L, P = 0.037 (Table 2).
For baseline pulmonary function, DLCO/VA% (decreased oxygen saturation vs. non decreased oxygen saturation): 77.0 (74.3, 93.6) % versus 89.5 (78.2, 97.4) %, P = 0.036. Patients with lower DLCO/VA% were more likely to have decreased oxygen saturation after infection with COVID-19. However, the remaining baseline pulmonary function measures were not statistically significantly different in predicting whether patients had a decrease in oxygen saturation after infection with COVID-19 (Table 2).
Results from the baseline 6MWD and SGRQ were also both correlated with whether patients had decreased oxygen saturation after infection with COVID-19. 6MWD (decreased oxygen saturation vs. non decreased oxygen saturation): 464 (406, 538) m versus 532 (470, 575) m, P = 0.028; total SGRQ score (decreased oxygen saturation vs. non decreased oxygen saturation): 46 (20, 64) versus 19 (8, 26), P = 0.009 (Table 2).
The baseline DSS of PAP patients better predicted the likelihood that PAP patients would have decreased oxygen saturation after COVID-19 infection. Patients with higher DSS, which means who suffered more severe disease with PAP, who were more likely to have decreased oxygen saturation after COVID-19 infection (P = 0.017) (Table 2).
In univariate analysis, DSS, LDH level and DLCO/VA% were all predictors of whether oxygen saturation decreased after infection with COVID-19. However, in multivariate analysis, only the DSS categories was independent predictor of whether oxygen saturation decreased in patients infected with COVID-19 in this cohort (≥ 3; OR 24.000; 95% CI 1.689–340.992; P = 0.019).
Symptoms and interventions after infection with COVID-19
After COVID-19 infection, patients may develop a variety of clinically relevant symptoms, the most frequent of which is fever, with 33 out of 39 patients (84.6%) experiencing fever after COVID-19 infection, followed by asthenia in 24 out of 39 (61.5%), expectoration in 20 out of 39 (51.3%), headache in 19 out of 39 (48.7%), pharyngalgia or cough in 18 out of 39 (46.2%), and a number of other COVID-19 relevant symptoms, including nasal congestion, rhinorrhea, hyposmia, hypogeusia, myalgia, and diarrhea, none of which correlated significantly with whether patients had decreased oxygen saturation. However, dyspnea symptoms were significantly correlated with decreased oxygen saturation (P < 0.001), with 7 out of 39 patients (17.9%) had new-onset dyspnea, 6 out of 39 patients (15.4%) had worsening dyspnea, and the remaining patients did not have dyspnea symptoms (Table 3).
Thirteen out of 39 patients (33.3%) had outpatient or emergency department visits after COVID-19 infection; 4 out of 39 (10.3%) were hospitalized, all of whom had decreased oxygen saturation, but none were admitted to the ICU. Six out of 39 patients (15.4%) required additional oxygen therapy or had increased oxygen conditions than before, all of whom were treated with nasal catheter oxygen therapy. Thirty-six out of 39 patients (92.3%) were taking NSAIDs or analgesics, including but not limited to acetaminophen, ibuprofen, and loxoprofen sodium; 9 out of 39 (23.1%) were taking antibiotics; 3 out of 39 (7.7%) were on systemic corticosteroids. Moreover, only 2 patients took antivirals for COVID-19, one for Azvudine and another for Nirmatrelvir/ritonavir. Patients with decreased oxygen saturation after COVID-19 infection were more likely to require oxygen therapy (P < 0.001) and to be taking systemic corticosteroids (P = 0.024) and antibiotic (P = 0.014) medications. For aPAP patients on GM-CSF inhalation therapy, 8 out of 13 (61.5%) of such patients continuously GM-CSF inhalation therapy after COVID-19 infection compared with 5 out of 13 (38.5%) who discontinued it. There was no significant difference in whether aPAP patients continuously used or discontinued GM-CSF inhalation therapy after COVID-19 infection on whether patients had a decrease in oxygen saturation (Table 3).
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