Alterations in the immune system persist after one year of convalescence in severe COVID-19 patients

Introduction Severe COVID-19 originates a myriad of alterations in the immune system during active disease, especially in the T and NK cell compartments, but several studies in the last year have unveiled some alterations that persist in convalescence. Although most of the studies follow the participants for a short recovery time, studies following patients up to three or six months still find alterations. We aimed at evaluating changes in the NK, T and B cell compartments after severe COVID-19 in participants with a median recovery time of eleven months. Methods Eighteen convalescent of severe COVID-19 (CSC), 14 convalescent of mild COVID-19 (CMC) and nine controls were recruited. NKG2A, NKG2C, NKG2D and the activating receptor NKp44 were evaluated in NKbright, NKdim and NKT subpopulations. In addition, CD3 and CD19 were measured and a basic biochemistry with IL-6 levels was obtained. Results CSC participants showed lower NKbright/NKdim ratio, higher NKp44 expression in NKbright subpopulations, higher levels of serum IL-6, lower levels of NKG2A+ T lymphocytes and a trend to a lower expression of CD19 in B lymphocytes compared to controls. CMC participants showed no significant alterations in the immune system compared to controls. Conclusions These results are concordant with previous studies, which find alterations in CSC weeks or months after resolution of the symptoms, and point to the possibility of these alterations lasting one year or more after COVID-19 resolution.

Alterations in the immune system persist after one year of convalescence in severe COVID-19 patients.

Introduction: Severe COVID-19 originates a myriad of alterations in the immune system during active disease, especially in the T and NK cell compartments, but several studies in the last year have unveiled some alterations that persist in convalescence. Although most of the studies follow the participants for a short recovery time, studies following patients up to three or six months still find alterations. We aimed at evaluating changes in the NK, T and B cell compartments after severe COVID-19 in participants with a median recovery time of eleven months. Methods: Eighteen convalescent of severe COVID-19 (CSC), 14 convalescent of mild COVID-19 (CMC) and nine controls were recruited. NKG2A, NKG2C, NKG2D and the activating receptor NKp44 were evaluated in NKbright, NKdim and NKT subpopulations. In addition, CD3 and CD19 were measured and a basic biochemistry with IL-6 levels was obtained. Results: CSC participants showed lower NKbright/NKdim ratio, higher NKp44 expression in NKbright subpopulations, higher levels of serum IL-6, lower levels of NKG2A+ T lymphocytes and a trend to a lower expression of CD19 in B lymphocytes compared to controls. CMC participants showed no significant alterations in the immune system compared to controls. Conclusions: These results are concordant with previous studies, which find alterations in CSC weeks or months after resolution of the symptoms, and point to the possibility of these alterations lasting one year or more after COVID-19 resolution.

Severe COVID-19 Illness and α1-Antitrypsin Deficiency: COVID-AATD Study.

BACKGROUND: Epidemiologic studies have reported that the geographical distribution of the prevalence of allelic variants of serine protein inhibitor-A1 (SERPINA1) and severe cases of COVID-19 were similar. METHODS: A multicenter, cross-sectional, observational study to evaluate the frequency of alpha-1 antitrypsin deficiency (AATD) in patients with COVID-19 and whether it was associated with having suffered severe COVID-19. RESULTS: 2022 patients who had laboratory-confirmed SARS-CoV-2 infection. Mutations associated with AATD were more frequent in severe COVID versus non-severe (23% vs. 18.8%, p = 0.022). The frequency of Pi*Z was 37.8/1000 in severe COVID versus 17.5/1000 in non-severe, p = 0.001. Having an A1AT level below 116 was more frequent in severe COVID versus non-severe (29.5% vs. 23.1, p = 0.003). Factors associated with a higher likelihood of severe COVID-19 were being male, older, smoking, age-associated comorbidities, and having an A1AT level below 116 mg/dL [OR 1.398, p = 0.003], and a variant of the SERPINA1 gene that could affect A1AT protein [OR 1.294, p = 0.022]. CONCLUSIONS: These observations suggest that patients with AATD should be considered at a higher risk of developing severe COVID-19. Further studies are needed on the role of A1AT in the prognosis of SARS-CoV-2 infection and its possible therapeutic role.

COVID-19's impact on care practice for alpha-1-antitrypsin deficiency patients.

BACKGROUND: Patients with alpha-1 antitrypsin deficiency (AATD), commonly categorized as a rare disease, have been affected by the changes in healthcare management brought about by COVID-19. This study's aim was to identify the changes that have taken place in AATD patient care as a result of the COVID-19 pandemic in Spain and to propose experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. METHODS: A qualitative descriptive case study with a holistic single-case design was conducted, using focus groups with experts in AATD clinical management, including 15 health professionals with ties to the Spanish health system (12 pneumologists and 2 hospital pharmacists from 11 different hospitals in Spain) and 1 patient representative. RESULTS: COVID-19 has had a major impact on numerous aspects of AATD clinical patient management in Spain, including diagnostic, treatment, and follow-up phases. The experts concluded that there is a need to strengthen coordination between Primary Care and Hospital Care and improve the coordination processes across all the organizations and actors involved in the healthcare system. Regarding telemedicine and telecare, experts have concluded that it is necessary to promote this methodology and to develop protocols and training programs. Experts have recommended developing personalized and precision medicine, and patient participation in decision-making, promoting self-care and patient autonomy to optimize their healthcare and improve their quality of life. The possibility of monitoring and treating AATD patients from home has also been proposed by experts. Another result of the study was the recommendation of the need to ensure that plasma donations are made on a regular basis by a sufficient number of healthy individuals. CONCLUSION: The study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation.

Association of anti-SARS-COV-2 vaccine with increased incidence of myositis-related anti-RNA-synthetases auto-antibodies.

Introduction: SARS-CoV-2 is a RNA virus that associates with heterogeneous clinical manifestations and complications. Auto-antibodies are identified in approximately 50% of hospitalized COVID-19 patients. Objectives: To determine the global incidence of myositis-related auto-antibodies (non Jo1-RNA synthetases: anti-PL7, anti-PL12, anti-EJ, anti-OJ and RNA-sensor: anti-MDA5) in our laboratory during COVID-19 pandemics, and to describe the clinical and laboratory features of these patients. Study design: A retrospective study was performed from 2015 to 2021 in a cohort of 444 patients with suspected inflammatory myopathy. The incidence of positive results for the MSA was expressed as absolute value per year for the reference population. Immunoblot analysis, indirect immunofluorescence and HLA typing of 36 patients with positivity for MSAs were collected and analyzed. Results: We observed MSA positive in 28 patients in 2020 and 36 patients in 2021, representing a mean increase of 6-fold respect to previous years since 2015 (range, 0 to 19). In 2020, the most common antibody detected was anti-MDA5 (68%). In contrast, in 2021 the most common antibodies were anti-PL7 and/or anti-PL12 (69%). All patients in 2021 with positive anti-synthetases were fully vaccinated, 4 had previous documented infection, with median time from vaccine to MSA positivity of 5 months. Eight out of 36 patients (22%) reported clinical onset after SARS-CoV-2 vaccination and 6 out of 36 (17%) presented clinical and/or radiological worsening after SARS-CoV-2 vaccination. All patients presented with a known human leukocyte antigen (HLA)-DRB1* allele associated with ASS. The most prevalent alleles identified were DRB1*03:01, DRB1*04, DRB1*11:01, corresponding to 70% (16/23) of our cohort. Conclusions: Our preliminary data show an increased incidence of anti-synthetase antibodies during COVID-19 pandemic and SARS-CoV-2 vaccination associated to HLA DRB1* risk allele. Differential profiles of MSA specificities were observed: mainly against RNA-sensors in 2020 and against RNA-synthetases in 2021. Further studies are needed to support the association between SARS-CoV-2 infection and/or vaccination and the occurrence of this autoimmune syndrome.

Long-term Outcomes and Recovery of Patients who Survived COVID-19: LUNG INJURY COVID-19 Study.

Background: LUNG INJURY COVID-19 (clinicaltrials.gov NCT 21/399-E) is a registry-based prospective observational cohort study to evaluate long-term outcomes and recovery 12 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection according to severity. Methods: Three hundred five coronavirus disease 2019 (COVID-19) survivors were included (moderate, 162; severe, 143). Twelve months after SARS-CoV-2 infection, there was resolution of respiratory symptoms (37.9% in severe vs 27.3% in moderate pneumonia; P = .089). Results: Exertional dyspnea was present (20% in severe vs 18.4% in moderate; P = .810). Abnormalities on chest radiology imaging were detected more often in severe COVID-19 infection vs moderate infection (29% vs 8.8%; P < .001). Pulmonary function testing (forced spirometry or diffusion) performed at 12 months of mean follow-up according to protocol detected anomalies in 31.4% of patients with severe COVID-19 courses and in 27.7% of moderate patients. Risk factors associated with diffusion impairment at 12 months were age (odds ratio [OR], 1.05; 95% CI, 1.01-1.10; P = .008), forced expiratory volume in 1 second predicted at follow-up (OR, 0.96; 95% CI, 0.93-0.99; P = .017), and dyspnea score at follow-up (OR, 3.16; 95% CI, 1.43-6.97; P = .004). Computed tomography (CT) scans performed at 12 months of mean follow-up showed evidence of fibrosis in almost half of patients with severe COVID-19 courses, who underwent CT according to protocol. Conclusions: At 12 months from infection onset, most patients refer to symptoms, particularly muscle weakness and dyspnea, and almost one-third of patients with severe COVID-19 pneumonia had impaired pulmonary diffusion and abnormalities on chest radiology imaging. These results emphasize the importance of systematic follow-up after severe COVID-19, with appropriate management of pulmonary sequelae.

Long-term outcomes and recovery of patients who survived COVID-19: LUNG INJURY COVID-19 Study

Introduction LUNG INJURY COVID-19 (clinicaltrials.gov NCT 21/399-E) is a registry-based prospective observational cohort study to evaluate long-term outcomes and recovery 12 months after SARS-CoV-2 infection according to severity. Results 305 COVID-19 survivors were included (moderate: 162, severe: 143). 12 months after SARS-CoV-2 infection, there was resolution of respiratory symptoms (37.9% in severe versus 27.3% in moderate pneumonia;p = 0.089). Exertional dyspnea was present (20% in severe vs 18.4% in moderate, p = 0.810). Abnormalities in chest radiology imaging were detected in severe COVID-19 infection versus moderate infection (29% versus 8.8%;p <0.001). Pulmonary function testing (forced spirometry or diffusion) performed at 12 months of mean follow-up according to protocol detected anomalies in 31.4% of patients with severe COVID-19 courses and in 27.7% of moderate patients. Risk factors associated with diffusion impairment at 12 months were age (OR: 1.05, 95% CI: 1.01-1.10, p = 0.008), FEV1% predicted at follow-up (OR: 0.96, 95% CI: 0.93-0.99, p = 0.017) and dyspnea score at follow-up (OR: 3.16, 95% CI: 1.43-6.97, p = 0.004). CT scans performed at 12 months of mean follow-up showed evidence of fibrosis in almost half of patients with severe COVID-19 courses, who underwent CT according to protocol. Conclusions At 12 months from infection onset, most patients refer to symptoms, particularly muscle weakness and dyspnea, and almost one third of patients with severe COVID-19 pneumonia had impaired pulmonary diffusion and abnormalities in chest radiology imaging. These results emphasize the importance of a systematic follow-up after severe COVID-19, with appropriate management of pulmonary sequelae.