Mucosal immune response after the booster dose of the BNT162b2 COVID-19 vaccine.

BACKGROUND: To date, only a few studies reported data regarding the development of mucosal immune response after the BNT162b2-booster vaccination. METHODS: Samples of both serum and saliva of 50 healthcare workers were collected at the day of the booster dose (T3) and after two weeks (T4). Anti-S1-protein IgG and IgA antibody titres and the neutralizing antibodies against the Wuhan wild-type Receptor-Binding Domain in both serum and saliva were measured by quantitative and competitive ELISA, respectively. Data were compared with those recorded after the primary vaccination cycle (T2). Neutralizing antibodies against the variants of concern were measured in those individuals with anti-Wuhan neutralizing antibodies in their saliva. FINDINGS: After eight months from the second dose, IgG decreased in both serum (T2GMC: 23,838.5 ng/ml; T3GMC: 1473.8 ng/ml) and saliva (T2GMC: 12.9 ng/ml; T3GMC: 0.3 ng/ml). Consistently, serum IgA decreased (T2GMC: 48.6 ng/ml; T3GMC: 6.4 ng/ml); however, salivary IgA showed a different behaviour and increased (T2GMC: 0.06 ng/ml; T3GMC: 0.41 ng/ml), indicating a delayed activation of mucosal immunity. The booster elicited higher titres of both IgG and IgA when compared with the primary cycle, in both serum (IgG T4GMC: 98,493.9 ng/ml; IgA T4GMC: 187.5 ng/ml) and saliva (IgG T4GMC: 21.9 ng/ml; IgA T4GMC: 0.65 ng/ml). Moreover, the booster re-established the neutralizing activity in the serum of all individuals, not only against the Wuhan wild-type antigen (N = 50; INH: 91.6%) but also against the variants (Delta INH: 91.3%; Delta Plus INH: 89.8%; Omicron BA.1 INH: 85.1%). By contrast, the salivary neutralizing activity was high against the Wuhan antigen in 72% of individuals (N = 36, INH: 62.2%), but decreased against the variants, especially against the Omicron BA.1 variant (Delta N = 27, INH: 43.1%; Delta Plus N = 24, INH: 35.2%; Omicron BA.1 N = 4; INH: 4.7%). This was suggestive for a different behaviour of systemic immunity observed in serum with respect to mucosal immunity described in saliva (Wald chi-square test, 3 df of interaction between variants and sample type = 308.2, p < 0.0001). INTERPRETATION: The BNT162b2-booster vaccination elicits a strong systemic immune response but fails in activating an effective mucosal immunity against the Omicron BA.1 variant. FUNDING: This work was funded by the Department of Medicine and Surgery, University of Insubria, and supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020), Italy.

Detection of Torquetenovirus and Redondovirus DNA in Saliva Samples from SARS-CoV-2-Positive and -Negative Subjects.

OBJECTIVES: Torquetenovirus (TTV) and Redondovirus (ReDoV) are the most prevalent viruses found in the human respiratory virome in viral metagenomics studies. A large-scale epidemiological study was performed to investigate their prevalence and loads in saliva samples according to SARS-CoV-2 status. METHODS: Saliva samples from 448 individuals (73% SARS-CoV-2 negative and 27% SARS-CoV-2 positive) aged 23-88 years were tested. SARS-CoV-2 and TTV were determined in saliva by specific qualitative and quantitative real-time PCRs, respectively. A sub-cohort of 377 subjects was additionally tested for the presence and load of ReDoV in saliva, and a different sub-cohort of 120 subjects for which paired saliva and plasma samples were available was tested for TTV and ReDoV viremia at the same timepoints as saliva. RESULTS: TTV in saliva was 72% prevalent in the entire cohort, at a mean DNA load of 4.6 log copies/mL, with no difference regardless of SARS-CoV-2 status. ReDoV was found in saliva from 61% of the entire cohort and was more prevalent in the SARS-CoV-2-negative subgroup (65% vs. 52%, respectively). In saliva, the total mean load of ReDoV was very similar to the one of TTV, with a value of 4.4 log copies/mL. The mean viral loads in subjects infected with a single virus, namely, those infected with TTV or ReDoV alone, was lower than in dually infected samples, and Tukey's multiple-comparison test showed that ReDoV single-infected samples resulted in the only true outlier (p = 0.004). Differently from TTV, ReDoV was not detected in any blood samples. CONCLUSIONS: This study establishes the prevalence and mean value of TTV and ReDoV in saliva samples and demonstrates the existence of differences between these two components of the human virome.

Interleukin-1 and the NLRP3 inflammasome in COVID-19: Pathogenetic and therapeutic implications.

A hyperinflammatory response during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection crucially worsens clinical evolution of coronavirus disease 2019 (COVID-19). The interaction between SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) triggers the activation of the NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Enhanced inflammasome activity has been associated with increased disease severity and poor prognosis. Evidence suggests that inflammasome activation and interleukin-1ß (IL-1ß) release aggravate pulmonary injury and induce hypercoagulability, favoring progression to respiratory failure and widespread thrombosis eventually leading to multiorgan failure and death. Observational studies with the IL-1 blockers anakinra and canakinumab provided promising results. In the SAVE-MORE trial, early treatment with anakinra significantly shortened hospital stay and improved survival in patients with moderate-to-severe COVID-19. In this review, we summarize current evidence supporting the pathogenetic role of the NLRP3 inflammasome and IL-1ß in COVID-19, and discuss clinical trials testing IL-1 inhibition in COVID-19.

Lesson Learnt by Covid-19: Going from Pandemic to Endemic Covid-19, should we Work for Diagnostic Criteria to Perform a Right Diagnosis of Covid-19 in the Future?

Patients with lung failure could be always easily identified because associated to typical signs and symptoms have anamnestic relevant data (e.g. immunocompromised patients or antivax people or non-responders to vaccines);yet also patients without recent clinical findings of lung failure may be found with interstitial pneumonia that should be investigated with a thorough differential diagnosis including also the research of SARS CoV2 on nasopharyngeal swab or bronchoalveolar lavage. Immunological tests as immunoglobulin's toward SARS CoV2 IG M or IG G have a positive clinical impact only if symptoms are longer than 5-6 days and in non-vaccinated people (in particular IG G). [...]in patients with high suspect of COVID-19radiological imaging of lung is always needed because the specific tropism of SARS CoV2 for respiratory system, in particular for the action of viral spike protein and its link with ACE2 protein present in high concentration on the surface of cells of respiratory tract. [...]these patients may induce clinical misunderstanding in daily clinical practice: they may refer a specific symptoms escaping each type of triage system, they may have a reduced or absent viral load so escaping real Time PCR at NPS and they may show not-extended interstitial pneumonia without recent infection and/or lung failure so inducing all of us to consider a thorough differential diagnosis with other causes of interstitial pneumonia. [...]after the exclusion of connettivitiis (e.g. rheumatoid arthritis, systemic erythematous lupus and so) [30] and hypersensitivity pneumonitis (e.g. drug intolerance, allergy and so on) [31, 32], an evaluation of infective causes should be performed and it should include the microbiological test to identify bacteria, pests or viruses (e.g. mycoplasma, legionellaspp, pneumocystis, influenza virus) [33, 34] and to include also the research of SARS CoV2 with NPS or bronchoalveolar lavage (BAL) with real time PCR (Table 1).

Correlation of SpO2/FiO2 and PaO2/FiO2 in patients with symptomatic COVID-19: An observational, retrospective study.

Some patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience acute hypoxemic respiratory failure progressing toward atypical acute respiratory distress syndrome (ARDS). The aim of the study is to evaluate whether a correlation between ratio of peripheral saturation of oxygen (SpO2) and fraction of inspired oxygen (S/F) and ratio of arterial partial pressure of oxygen and fraction of inspired oxygen (P/F) exists in COVID-19-related ARDS as already known in classical ARDS. In this multicenter, retrospective, observational study, consecutive, adult (≥ 18 years) patients with symptomatic coronavirus disease 2019 (COVID-19) admitted to different COVID-19 divisions in Italy between March and December 2020 were included. Patients with SpO2 > 97% or missing information were excluded. We included 1,028 patients (median age 72 years, prevalence of males [62.2%]). A positive correlation was found between P/F and S/F (r = 0.938, p < 0.0001). A receiver operating characteristic (ROC) curve analysis showed that S/F accurately recognizes the presence of ARDS (P/F ≤ 300 mmHg) in COVID-19 patients, with a cut-off of ≤ 433% showing good sensitivity and specificity. S/F was also tested against P/F values ≤ 200 and ≤ 100 mmHg (suggestive for moderate and severe ARDS, respectively), the latter showing great accuracy for S/F ≤ 178%. S/F was accurate in predicting ARDS for SpO2 ≥ 92%. In conclusion, our findings support the routine use of S/F as a reliable surrogate of P/F in patients with COVID-19-related ARDS.

Advances in pharmacotherapy for acute and recurrent pericarditis.

INTRODUCTION: Aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are first-line treatments for acute and recurrent pericarditis. Drugs blocking the NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome/interleukin-1ß (IL-1ß) axis are beneficial in patients with multiple recurrences. AREAS COVERED: In this review, the role of the NLRP3 inflammasome/IL-1ß axis in the pathophysiology of pericarditis is discussed. Updates about novel therapies targeting IL-1 for recurrent pericarditis (RP) and practical considerations for their use are provided. EXPERT OPINION: IL-1 inhibitors have been increasingly studied for RP in recent years. NLRP3 inflammasome is a key mediator in the pathophysiology of RP. IL-1ß, its main product, can sustain its own production and feeds local and systemic inflammation. Randomized clinical trials testing anakinra (a recombinant form of the IL-1 receptor antagonist blocking IL-1α and IL-1ß) and rilonacept (an IL-1α and IL-1ß trap) have shown that IL-1 blockade reduces recurrences. These trials also helped in phenotyping patients with RP. Patients with multiple recurrences and signs of pericardial and/or systemic inflammation might benefit from IL-1 blockers in order to interrupt cyclic flares of auto-inflammation. Given this evidence, guidelines should consider incorporating IL-1 blockers.

Colchicine for COVID-19: targeting NLRP3 inflammasome to blunt hyperinflammation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is capable of inducing the activation of NACHT, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome, a macromolecular structure sensing the danger and amplifying the inflammatory response. The main product processed by NLRP3 inflammasome is interleukin (IL)-1ß, responsible for the downstream production of IL-6, which has been recognized as an important mediator in coronavirus disease 2019 (COVID-19). Since colchicine is an anti-inflammatory drug with the ability to block NLRP3 inflammasome oligomerization, this may prevent the release of active IL-1ß and block the detrimental effects of downstream cytokines, i.e. IL-6. To date, few randomized clinical trials and many observational studies with colchicine have been conducted, showing interesting signals. As colchicine is a nonspecific inhibitor of the NLRP3 inflammasome, compounds specifically blocking this molecule might provide increased advantages in reducing the inflammatory burden and its related clinical manifestations. This may occur through a selective blockade of different steps preceding NLRP3 inflammasome oligomerization as well as through a reduced release of the main cytokines (IL-1ß and IL-18). Since most evidence is based on observational studies, definitive conclusion cannot be drawn and additional studies are needed to confirm preliminary results and further dissect how colchicine and other NLRP3 inhibitors reduce the inflammatory burden and evaluate the timing and duration of treatment.

Upper extremity deep vein thrombosis in COVID-19: Incidence and correlated risk factors in a cohort of non-ICU patients.

BACKGROUND: Venous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence. METHODS: We performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT. RESULTS: 257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1-14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, PaO2/FiO2, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33-26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41-9.78). CONCLUSIONS: UEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients.

A blue man standing

An 85-year-old was admitted in Internal Medic Ward for recurrent episodes of acute respiratory failure. His electrocardiogram showed a new onset of atrial flutter with spontaneous reversal to sinus rhythm (narrow QRS complex and normal atrioventricular conduction). The dyspnoea was worse with the patient sitting and was better when lying supine. Also, he report back pain associated to his major kyphoscoliosis. Results of chest radiography and blood test were normal. The arterial blood gas test revealed a hypocapnic hypoxemic respiratory failure, therefore the patient oxygen supplementation with noninvasive ventilation (NIV) was started, but peripheral oxygen saturation was persistently below 88% despite the high flow oxygenation. The patient underwent nasopharyngeal (NP) swab (ruling out SARS-CoV-2), high-resolution computed tomography (which was not pathologic), and computed tomography angiography (excluding pulmonary embolism). A transthoracic echocardiography was performed showing concentric hypertrophy, left atriomegaly and severe aortic ectasia of the root and of his ascending part, normal pulmonary pression and an aneurism of the interatrial septum with the presence of right-to-left shunt after using agitate saline contrast with Valsalva maneuver. Transesophageal echocardiography (TTE) confirmed the presence of severe structural interatrial septal abnormality with wide left convex aneurysm and an atrial septum defect (ASD) as ostium secundum, causing severe bidirectional shunt. Therefore, the patient underwent a successful transcatheter closure of secundum ASD with device Amplatzer Septal Occluder 018, while monitored with cardiac catheterization and transesophageal echocardiography. After few days, the patient was discharged at home without oxygen therapy. At the 3-month follow-up visit he reported no respiratory symptoms. Platypnea-orthodeoxia syndrome (POS) is an uncommon disorder characterized by dyspnoea and hypoxemia that occurs when the patient is sitting or standing and disappear quickly when recumbent. POS is characterized by both an anatomic and a functional component. The anatomic element is typically an interatrial communication such as ASD or Patent Foramen Ovale, which cause blood shunt left-to-right due to a higher pressure in left atrium and a greater compliance of the right ventricle, in the presence of normal pulmonary artery pressure. The syndrome occurs when a functional element, such as an increased atrial pressure or a decreased compliance of the right ventricle, reverses the flow. The shunts are often small and could remain asymptomatic: the high left atrial pressure let the defect close until there is a reverse pression which stretched atrial septum in particular in the upright position. In fact, when the patient is standing, the inferior vena cava comes in line with the defect increasing the right-to-left flow, sparking the respiratory symptoms. This could be linked to a cardiac or an extracardiac condition;in this case the presence of kyphoscoliosis and severe aortic ectasia of the root and of his ascending part, played an important role. The diagnosis is mainly made by echocardiography and cardiac catheterization to verify the mismatch in oxygen saturation between the pulmonary vein and the aorta. The diagnosis of POS is challenging, often considered only after other possible diagnosis is excluded. When POS is triggered by an interatrial defect in the absence of severe pulmonary hypertension, the usual treatment is a percutaneous or surgical closure.

Machine Learning to Calculate Heparin Dose in COVID-19 Patients with Active Cancer.

To realize a machine learning (ML) model to estimate the dose of low molecular weight heparin to be administered, preventing thromboembolism events in COVID-19 patients with active cancer. Methods: We used a dataset comprising 131 patients with active cancer and COVID-19. We considered five ML models: logistic regression, decision tree, random forest, support vector machine and Gaussian naive Bayes. We decided to implement the logistic regression model for our study. A model with 19 variables was analyzed. Data were randomly split into training (70%) and testing (30%) sets. Model performance was assessed by confusion matrix metrics on the testing data for each model as positive predictive value, sensitivity and F1-score. Results: We showed that the five selected models outperformed classical statistical methods of predictive validity and logistic regression was the most effective, being able to classify with an accuracy of 81%. The most relevant result was finding a patient-proof where python function was able to obtain the exact dose of low weight molecular heparin to be administered and thereby to prevent the occurrence of VTE. Conclusions: The world of machine learning and artificial intelligence is constantly developing. The identification of a specific LMWH dose for preventing VTE in very high-risk populations, such as the COVID-19 and active cancer population, might improve with the use of new training ML-based algorithms. Larger studies are needed to confirm our exploratory results.

Mucosal immune response in BNT162b2 COVID-19 vaccine recipients.

BACKGROUND: Although the BNT162b2 COVID-19 vaccine is known to induce IgG neutralizing antibodies in serum protecting against COVID-19, it has not been studied in detail whether it could generate specific immunity at mucosal sites, which represent the primary route of entry of SARS-CoV-2. METHODS: Samples of serum and saliva of 60 BNT162b2-vaccinated healthcare workers were collected at baseline, two weeks after the first dose and two weeks after the second dose. Anti-S1-protein IgG and IgA total antibodies titres and the presence of neutralizing antibodies against the Receptor Binding Domain in both serum and saliva were measured by quantitative and by competitive ELISA, respectively. FINDINGS: Complete vaccination cycle generates a high serum IgG antibody titre as a single dose in previously infected seropositive individuals. Serum IgA concentration reaches a plateau after a single dose in seropositive individuals and two vaccine doses in seronegative subjects. After the second dose IgA level was higher in seronegative than in seropositive subjects. In saliva, IgG level is almost two orders of magnitude lower than in serum, reaching the highest values after the second dose. IgA concentration remains low and increases significantly only in seropositive individuals after the second dose. Neutralizing antibody titres were much higher in serum than in saliva. INTERPRETATION: The mRNA BNT162b2 vaccination elicits a strong systemic immune response by drastically boosting neutralizing antibodies development in serum, but not in saliva, indicating that at least oral mucosal immunity is poorly activated by this vaccination protocol, thus failing in limiting virus acquisition upon its entry through this route. FUNDING: This work was funded by the Department of Medicine and Surgery, University of Insubria, and partially supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020).

Advanced robotics as a support in healthcare organizational response: A COVID-19 pandemic case study.

The use of robotics is becoming widespread in healthcare. However, little is known about how robotics can affect the relationship with patients during an emergency or how it impacts clinicians in their organization and work. As a hospital responding to the consequences of the COVID-19 pandemic "ASST dei Sette Laghi" (A7L) in Varese, Italy, had to react quickly to protect its staff from infection while coping with high budgetary pressure as prices of Personal Protection Equipment (PPE) increased rapidly. In response, it introduced six semi-autonomous robots to mediate interactions between staff and patients. Thanks to the cooperation of multiple departments, A7L implemented the solution in less than 10 weeks. It reduced risks to staff and outlay for PPE. However, the characteristics of the robots affected staff's perceptions. This case study reviews critical issues faced by A7L in introducing these devices and recommendations for the path forward.

Spike protein evolution in the SARS-CoV-2 Delta variant of concern: a case series from Northern Lombardy.

The SARS-CoV-2 variant of concern (VOC) "Delta" is currently defined by PANGOLIN as a cluster of 33 different AY sublineages. Delta (in particular B.1.617.2) is largely and rapidly replacing the Alpha VOC as the dominant clade in most countries. To date, variations in the Spike protein of the Delta VOC have largely been limited. We report here the results of a genomic surveillance programme from Northern Italy. We identified several Delta sublineages harbouring mutations previously reported in GISAID at extremely low frequencies and in different combinations. Two patients (one of them vaccinated) tested positive for a Delta sublineage harbouring S71F, T250I, T572I and K854N. More patients tested positive for G769 V plus C1248F, A352S, and R158G and C1248F, respectively. Genomic surveillance of Delta variants should be encouraged to anticipate immune escape and deploy countermeasures.

Emergence of SARS-COV-2 Spike Protein Escape Mutation Q493R after Treatment for COVID-19.

We report in vivo selection of a severe acute respiratory syndrome coronavirus 2 spike mutation (Q493R) conferring simultaneous resistance to bamlanivimab and etesivimab. This mutation was isolated from a patient who had coronavirus disease and was treated with these drugs.

Ferritin as prognostic marker in COVID-19: the FerVid study.

BACKGROUND: In COVID-19 patients the progressive clinical deterioration seems secondary to the activation of a cytokine storm. Ferritin is considered a direct mediator of the immune system and some evidences suggested a shared physio-pathogenic basis between COVID-19 and 'Hyperferritinemic Syndromes.' The aim of our study was to evaluate the prognostic role of ferritin in COVID-19 patients. METHODS: We retrospectively studied consecutive COVID-19 patients admitted to four Italian Internal Medicine Units. Role of potential prognostic markers was evaluated with binary logistic regression analysis and results were expressed as odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Poor outcome was defined as death or need to transfer in the intensive care unit. RESULTS: Two hundred patients were included (mean age 68.75 ± 13.22 years). Ferritin value was highly elevated (>3000 ng/mL) in 8% of our population; 13% of patients were transferred to intensive care units and 12% of patients died. At multivariate analysis, highly elevated ferritin levels (OR 16.67 C.I. 4.89-57.57 p < 0.001) and hemoglobin < 10 g/dL (OR 8.88 C.I. 2.02-39.09 p = 0.004) were independently associated with a bad outcome.Patients with ferritin values > 3000 ng/ml appeared to have an inflammatory activation with elevated values of CRP and D-dimer and low values of lymphocyte count. CONCLUSION: Our results confirm the prognostic role of ferritin in hospitalized COVID-19 patients. Patients with high ferritin levels should be considered critically ill and treated in an adequate setting. Furthermore, COVID-19 seems to share some characteristics with hyperferritinemic syndromes with potential therapeutic implications.

Lung Function and Symptoms in Post-COVID-19 Patients: A Single-Center Experience.

OBJECTIVE: To address the lack of information about clinical sequelae of coronavirus disease 2019 (COVID-19). PATIENTS AND METHODS: Previously hospitalized COVID-19 patients who were attending the outpatient clinic for post-COVID-19 patients (ASST Ovest Milanese, Magenta, Italy) were included in this retrospective study. They underwent blood draw for complete blood count, C-reactive protein, ferritin, D-dimer, and arterial blood gas analysis and chest high-resolution computed tomography (HRCT) scan. The primary endpoint was the assessment of blood gas exchanges after 3 months. Other endpoints included the assessment of symptoms and chest HRCT scan abnormalities and changes in inflammatory biomarkers after 3 months from hospital admission. RESULTS: Eighty-eight patients (n = 65 men; 73.9%) were included. Admission arterial blood gas analysis showed hypoxia and hypocapnia and an arterial partial pressure of oxygen/fractional inspired oxygen ratio of 271.4 (interquartile range [IQR]: 238-304.7) mm Hg that greatly improved after 3 months (426.19 [IQR: 395.2-461.9] mm Hg, P<.001). Forty percent of patients were still hypocapnic after 3 months. Inflammatory biomarkers dramatically improved after 3 months from hospitalization. Fever, resting dyspnea, and cough were common at hospital admission and improved after 3 months, when dyspnea on exertion and arthralgias arose. On chest HRCT scan, more than half of individuals still presented with interstitial involvement after 3 months. Positive correlations between the interstitial pattern at 3 months and dyspnea on admission were found. C-reactive protein at admission was positively associated with the presence of interstitial involvement at follow-up. The persistence of cough was associated with presence of bronchiectasis and consolidation on follow-up chest HRCT scan. CONCLUSION: Whereas inflammatory biomarker levels normalized after 3 months, signs of lung damage persisted for a longer period. These findings support the need for implementing post-COVID-19 outpatient clinics to closely follow-up COVID-19 patients after hospitalization.

High-dose dexamethasone treatment for COVID-19 severe acute respiratory distress syndrome: a retrospective study.

Low-dose dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). We retrospectively analyzed the efficacy of high-dose dexamethasone in patients with COVID-19-related ARDS and evaluated factors affecting the composite outcome (death or invasive mechanical ventilation). From March 4th to April 1st 2020, 98 patients with COVID-19 pneumonia were included. Those who after at least 7 days from symptom onset presented a worsening of the respiratory function or of inflammatory biomarkers were started on intravenous high-dose dexamethasone (20 mg daily for 5 days, followed by 10 mg daily for 5 days). Most patients were males (62%) with a mean age of 69 years. Hypertension and cardiovascular disease (CVD) were prevalent. Following dexamethasone treatment, a significant improvement in PaO2/FiO2 (277.41 [178.5-374.8] mmHg vs. 146.75 [93.62-231.16] mmHg, p < 0.001), PaO2 (88.15 [76.62-112.0] mmHg vs. 65.65 [57.07-81.22] mmHg, p < 0.001), and SpO2 (96 [95-98]% vs. 94 [90-96]%, p < 0.001) was observed. A concomitant decrease in C-reactive protein and ferritin levels was found (132.25 [82.27-186.5] mg/L vs. 7.3 [3.3-24.2] mg/L and 1169 [665-2056] ng/mL vs. 874.0 [569.5-1434] ng/mL, respectively; p < 0.001 for both vs. baseline). CVD was found to increase the risk of the composite outcome (RR 7.64, 95% CI 1.24-47.06, p = 0.028). In hospitalized patients with COVID-19-related ARDS, high-dose dexamethasone rapidly improves the clinical status and decreases inflammatory biomarkers. CVD was found to increase the risk of the composite outcome. These data support the importance of randomized clinical trials with high-dose dexamethasone in COVID-19 patients.