Infection with SARS-CoV-2 Variants Is Associated with Different Long COVID Phenotypes.

COVID-19 has been associated with a broad range of long-term sequelae, commonly referred to as "long-COVID" or "post-COVID-19" syndrome. Despite an increasing body of literature, long COVID remains poorly characterized. We retrospectively analysed data from electronic medical records of patients admitted to the post-COVID-19 outpatient service of the Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy, between June 2020 and June 2021, 4-12 weeks after hospital discharge. A total of 428 patients, 41% women, median age 64 years, underwent a follow-up visit a median 53 days after hospital discharge. Overall, 76% patients reported at least one persistent symptom, including dyspnoea (37%), chronic fatigue (36%), insomnia (16%), visual disorders (13%) and brain fog (13%). Increasing oxygen support (OR 1.4, 95% CI 1.1-1.8), use of immunosuppressants (OR 6.4, 95% CI 1.5-28) and female sex (OR 1.8, 95% CI 1.1-2.9) were associated with a higher risk of long COVID symptoms. Comparison between symptomatic patients infected in the period March-December 2020 (prevalent circulation of wild-type SARS-CoV-2) with those infected in the period January-April 2021 (prevalent circulation of B.1.1.7 Alpha variant) showed a significant modification in the pattern of symptoms belonging to the neurological and cognitive/emotional categories. Our findings confirmed shortness of breath and chronic fatigue as the most frequent long COVID manifestations, while female sex and severe COVID-19 course were the main risk factors for developing lingering symptoms. SARS-CoV-2 variants may induce different long COVID phenotypes, possibly due to changes in cell tropism and differences in viral-host interaction.

Incidental discovery of interstitial lung disease: diagnostic approach, surveillance and perspectives.

The incidental discovery of pre-clinical interstitial lung disease (ILD) has led to the designation of interstitial lung abnormalities (ILA), a radiological entity defined as the incidental finding of computed tomography (CT) abnormalities affecting more than 5% of any lung zone. Two recent documents have redefined the borders of this entity and made the recommendation to monitor patients with ILA at risk of progression. In this narrative review, we will focus on some of the limits of the current approach, underlying the potential for progression to full-blown ILD of some patients with ILA and the numerous links between subpleural fibrotic ILA and idiopathic pulmonary fibrosis (IPF). Considering the large prevalence of ILA in the general population (7%), restricting monitoring only to cases considered at risk of progression appears a reasonable approach. However, this suggestion should not prevent pulmonary physicians from pursuing an early diagnosis of ILD and timely treatment where appropriate. In cases of suspected ILD, whether found incidentally or not, the pulmonary physician is still required to make a correct ILD diagnosis according to current guidelines, and eventually treat the patient accordingly.

The Role of the Multidisciplinary Health Care Team in the Management of Patients with Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterised by immune dysfunction, vascular damage and fibrosis affecting the skin and multiple internal organs. The clinical spectrum of SSc is wide and its manifestations may lead to severe morbidity and mortality, in addition to a great impact on patients' quality of life. Due to the multifaceted clinical manifestations of SSc, its management requires a combined expertise of different medical specialists to guarantee an adequate disease control and prevent organ complications. Multi-disciplinary teams (MDT), which are composed by physicians and other specialized health professionals, represent therefore a key element for the comprehensive management of SSc patients. Moreover, MTD can improve communication and patients' empowerment while the presence of dedicated nurses can help patients to ask questions about their condition. The scope of this narrative review is to analyse the available evidences regarding the role of MDT in the management of SSc patients, and how this holistic approach may improve different disease domains and the overall prognosis. MDT regarding the cardiovascular and lung complication are the more represented in literature, given the great impact in prognosis. Nonetheless, MDT have been shown to be fundamental also in other disease domains as they can intercept early manifestations, thus stratifying patients based on the individual risks in order to personalize patients' follow-up. MDTs may also minimize the treatment delay, enabling fast-track specialist referral. On the other hand, there are few trials specifically studying MDT in SSc and several authors have highlight the lack of standardization.

Clinical, radiological and pathological findings in patients with persistent lung disease following SARS-CoV-2 infection.

Some patients experience pulmonary sequelae after SARS-CoV-2 infection, ranging from self-limited abnormalities to major lung diseases. Morphological analysis of lung tissue may help our understanding of pathogenic mechanisms and help to provide consistent personalised management. The aim of this study was to ascertain morphological and immunomolecular features of lung tissue. Transbronchial lung cryobiopsy was carried out in patients with persistent symptoms and computed tomography suggestive of residual lung disease after recovery from SARS-CoV-2 infection. 164 patients were referred for suspected pulmonary sequelae after COVID-19; 10 patients with >5% parenchymal lung disease underwent lung biopsy. The histological pattern of lung disease was not homogeneous and three different case clusters could be identified, which was mirrored by their clinical and radiological features. Cluster 1 ("chronic fibrosing") was characterised by post-infection progression of pre-existing interstitial pneumonias. Cluster 2 ("acute/subacute injury") was characterised by different types and grades of lung injury, ranging from organising pneumonia and fibrosing nonspecific interstitial pneumonia to diffuse alveolar damage. Cluster 3 ("vascular changes") was characterised by diffuse vascular increase, dilatation and distortion (capillaries and venules) within otherwise normal parenchyma. Clusters 2 and 3 had immunophenotypical changes similar to those observed in early/mild COVID-19 pneumonias (abnormal expression of STAT3 in hyperplastic pneumocytes and PD-L1, IDO and STAT3 in endothelial cells). This is the first study correlating histological/immunohistochemical patterns with clinical and radiological pictures of patients with post-COVID lung disease. Different phenotypes with potentially different underlying pathogenic mechanisms have been identified.

The role of chest CT in deciphering interstitial lung involvement: systemic sclerosis versus COVID-19.

OBJECTIVE: The aim of this study was to identify the main CT features that may help in distinguishing a progression of interstitial lung disease (ILD) secondary to SSc from COVID-19 pneumonia. METHODS: This multicentric study included 22 international readers grouped into a radiologist group (RADs) and a non-radiologist group (nRADs). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. RESULTS: Fibrosis inside focal ground-glass opacities (GGOs) in the upper lobes; fibrosis in the lower lobe GGOs; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONs in the lower lobes (P < 0.0001) and signs of fibrosis in GGOs in the lower lobes (P < 0.0001) remained independently associated with COVID-19 pneumonia and SSc-ILD, respectively. A predictive score was created that was positively associated with COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity). CONCLUSION: CT diagnosis differentiating between COVID-19 pneumonia and SSc-ILD is possible through a combination of the proposed score and radiologic expertise. The presence of consolidation in the lower lobes may suggest COVID-19 pneumonia, while the presence of fibrosis inside GGOs may indicate SSc-ILD.

The SARS-CoV-2 viral load in COVID-19 patients is lower on face mask filters than on nasopharyngeal swabs.

Face masks and personal respirators are used to curb the transmission of SARS-CoV-2 in respiratory droplets; filters embedded in some personal protective equipment could be used as a non-invasive sample source for applications, including at-home testing, but information is needed about whether filters are suited to capture viral particles for SARS-CoV-2 detection. In this study, we generated inactivated virus-laden aerosols of 0.3-2 microns in diameter (0.9 µm mean diameter by mass) and dispersed the aerosolized viral particles onto electrostatic face mask filters. The limit of detection for inactivated coronaviruses SARS-CoV-2 and HCoV-NL63 extracted from filters was between 10 to 100 copies/filter for both viruses. Testing for SARS-CoV-2, using face mask filters and nasopharyngeal swabs collected from hospitalized COVID-19-patients, showed that filter samples offered reduced sensitivity (8.5% compared to nasopharyngeal swabs). The low concordance of SARS-CoV-2 detection between filters and nasopharyngeal swabs indicated that number of viral particles collected on the face mask filter was below the limit of detection for all patients but those with the highest viral loads. This indicated face masks are unsuitable to replace diagnostic nasopharyngeal swabs in COVID-19 diagnosis. The ability to detect nucleic acids on face mask filters may, however, find other uses worth future investigation.

Laryngotracheal aspiration test reduce the false negative rate in patients with suspected SARS-COV-2 pneumonia despite a negative nasopharyngeal swab.

BACKGROUND: In the emergency department (ED) definitive diagnosis of SARS-COV-2 pneumonia is challenging as nasopharyngeal swab (NPS) can give false negative results. Strategies to reduce false negative rate of NPS have limitations. Serial NPSs (24-48 h from one another) are time-consuming, sputum can not be collected in the majority of patients, and bronchoalveolar lavage (BAL), the most sensitive test, requires specific expertise. Laryngotracheal aspiration (LTA) is easy to perform and showed a similar accuracy to BAL for diagnosis of other pulmonary diseases, however it was not studied to diagnose SARS-COV-2 pneumonia. OBJECTIVE: An observational cross-sectional study was performed to evaluate the negative predictive value of LTA in patients with suspected SARS-COV-2 pneumonia despite a negative NPS. METHODS: In the EDs of two university hospitals, consecutive patients with suspected SARS-COV-2 pneumonia despite a negative NPS underwent LTA performed with a nasotracheal tube connected to a vacuum system. Final diagnosis based on all respiratory specimen tests (NPS, LTA and BAL) and hospital data was established by two reviewers and in case of discordance by a third reviewer. RESULTS: 117 patients were enrolled. LTA was feasible in all patients and no patients experienced adverse events. Fifteen (12.7%) patients were diagnosed with community-acquired SARS-COV-2 pneumonia: 13 LTA positive and only 2 (1.7%) LTA negative. The negative predictive value of NPS and LTA was 87.3% (79.9% - 92.7%) and 98.1% (93.3%99.8%) respectively. CONCLUSIONS: LTA resulted feasible, safe and reduced false negative rate in patients with suspected SARS-COV-2 pneumonia despite a negative NPS.

Assessing coronavirus disease 2019 (COVID-19) transmission to healthcare personnel: The global ACT-HCP case-control study.

OBJECTIVE: To characterize associations between exposures within and outside the medical workplace with healthcare personnel (HCP) SARS-CoV-2 infection, including the effect of various forms of respiratory protection. DESIGN: Case-control study. SETTING: We collected data from international participants via an online survey. PARTICIPANTS: In total, 1,130 HCP (244 cases with laboratory-confirmed COVID-19, and 886 controls healthy throughout the pandemic) from 67 countries not meeting prespecified exclusion (ie, healthy but not working, missing workplace exposure data, COVID symptoms without lab confirmation) were included in this study. METHODS: Respondents were queried regarding workplace exposures, respiratory protection, and extra-occupational activities. Odds ratios for HCP infection were calculated using multivariable logistic regression and sensitivity analyses controlling for confounders and known biases. RESULTS: HCP infection was associated with non-aerosol-generating contact with COVID-19 patients (adjusted OR, 1.4; 95% CI, 1.04-1.9; P = .03) and extra-occupational exposures including gatherings of ≥10 people, patronizing restaurants or bars, and public transportation (adjusted OR range, 3.1-16.2). Respirator use during aerosol-generating procedures (AGPs) was associated with lower odds of HCP infection (adjusted OR, 0.4; 95% CI, 0.2-0.8, P = .005), as was exposure to intensive care and dedicated COVID units, negative pressure rooms, and personal protective equipment (PPE) observers (adjusted OR range, 0.4-0.7). CONCLUSIONS: COVID-19 transmission to HCP was associated with medical exposures currently considered lower-risk and multiple extra-occupational exposures, and exposures associated with proper use of appropriate PPE were protective. Closer scrutiny of infection control measures surrounding healthcare activities and medical settings considered lower risk, and continued awareness of the risks of public congregation, may reduce the incidence of HCP infection.

Predictors of Worse Prognosis in Young and Middle-Aged Adults Hospitalized with COVID-19 Pneumonia: A Multi-Center Italian Study (COVID-UNDER50).

Obesity as well as metabolic and cardiovascular comorbidities are established, significant predictors of worse prognosis in the overall COVID-19 population, but limited information is available on their roles in young and middle-aged adults (aged ≤ 50 years). The main objectives of the present Italian multi-center study were to describe clinical characteristics and role of selected prognostic predictors in a large cohort of young and middle-aged hospitalized patients. Nine pulmonology units, across north and center of Italy, were involved in this retrospective study. Comorbidities were classified according to their known or potential association with COVID-19. A total of 263 subjects were included. The prevalence of obesity was 25.9%, mechanical ventilation (MV) was needed in 27.7%, and 28 in-hospital deaths occurred (10.6%). Obesity and older age were the only independent, significant predictors for MV. Comorbidities, such as hypertension, diabetes, asthma, and increased D-dimer levels were significantly associated with higher mortality risk, regardless of age, body mass index, and MV. Obesity in young and middle-aged adults is a strong predictor of a more complicated COVID-19, without, however, evidence of a significant effect on in-hospital mortality. Selected comorbidities, including hypertension, diabetes and asthma, significantly impact survival even in a younger population, suggesting the need for prompt recognition of these conditions.

Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia.

BACKGROUND: In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality. METHODS: We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. RESULTS: Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ±â€…9.0 vs 17.5 ±â€…12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84). CONCLUSION: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.