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.

COVID-19-Associated Pneumonia in a B-Cell-Depleted Patient With Non-Hodgkin Lymphoma: Recovery With Hyperimmune Plasma.

Coronavirus disease 2019 (COVID-19) can have a severe course in immunocompromised hosts and patients with hematological malignancies. In some cases, the bad prognosis is associated with the lack of B lymphocytes, with impaired antibody production and inefficient viral clearance. We report a case of a 67-year-old woman with a story of non-Hodgkin lymphoma treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), who got a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while being totally depleted of B cells. This condition has determined a severe and prolonged course of COVID-19, with persistently positive nasopharyngeal molecular swabs and lack of anti-SARS-CoV-2 specific antibodies. The clinical recovery was favored by the administration of convalescent hyperimmune plasma.

Immunotherapy of COVID-19: Inside and Beyond IL-6 Signalling.

Acting on the cytokine cascade is key to preventing disease progression and death in hospitalised patients with COVID-19. Among anti-cytokine therapies, interleukin (IL)-6 inhibitors have been the most used and studied since the beginning of the pandemic. Going through previous observational studies, subsequent randomised controlled trials, and meta-analyses, we focused on the baseline characteristics of the patients recruited, identifying the most favourable features in the light of positive or negative study outcomes; taking into account the biological significance and predictivity of IL-6 and other biomarkers according to specific thresholds, we ultimately attempted to delineate precise windows for therapeutic intervention. By stimulating scavenger macrophages and T-cell responsivity, IL-6 seems protective against viral replication during asymptomatic infection; still protective on early tissue damage by modulating the release of granzymes and lymphokines in mild-moderate disease; importantly pathogenic in severe disease by inducing the proinflammatory activation of immune and endothelial cells (through trans-signalling and trans-presentation); and again protective in critical disease by exerting homeostatic roles for tissue repair (through cis-signalling), while IL-1 still drives hyperinflammation. IL-6 inhibitors, particularly anti-IL-6R monoclonal antibodies (e.g., tocilizumab, sarilumab), are effective in severe disease, characterised by baseline IL-6 concentrations ranging from 35 to 90 ng/mL (reached in the circulation within 6 days of hospital admission), a ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2) between 100 and 200 mmHg, requirement of high-flow oxygen or non-invasive ventilation, C-reactive protein levels between 120 and 160 mg/L, ferritin levels between 800 and 1600 ng/mL, D-dimer levels between 750 and 3000 ng/mL, and lactate dehydrogenase levels between 350 and 500 U/L. Granulocyte-macrophage colony-stimulating factor inhibitors might have similar windows of opportunity but different age preferences compared to IL-6 inhibitors (over or under 70 years old, respectively). Janus kinase inhibitors (e.g., baricitinib) may also be effective in moderate disease, whereas IL-1 inhibitors (e.g., anakinra) may also be effective in critical disease. Correct use of biologics based on therapeutic windows is essential for successful outcomes and could inform future new trials with more appropriate recruiting criteria.

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.

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.

Suspected myocarditis in patients with COVID-19: A multicenter case series.

ABSTRACT: Although myocarditis can be a severe cardiac complication of COVID-19 patients, few data are available in the literature about the incidence and clinical significance in patients affected by SARS-CoV-2. This study aims to describe the prevalence and the clinical features of suspected myocarditis in 3 cohorts of patients hospitalized for COVID-19. We retrospectively evaluated all the consecutive patients admitted for COVID-19 without exclusion criteria. Suspect myocarditis was defined according to current guidelines. Age, sex, in-hospital death, length of stay, comorbidities, serum cardiac markers, interleukin-6, electrocardiogram, echocardiogram, and therapy were recorded. Between March 4 to May 20, 2020, 1169 patients with COVID-19 were admitted in 3 Italian Medicine wards. 12 patients (1%) had suspected acute myocarditis; 5 (41.7%) were men, mean age was 76 (SD 11.34; median 78.5 years); length of stay was 38 days on average (SD 8, median value 37.5); 3 (25%) patients died. 8 (66.7%) had a history of cardiac disease; 7 (58.33%) patients had other comorbidities like diabetes, chronic obstructive pulmonary disease, or renal insufficiency. Myocarditis patients had no difference in sex prevalence, rate of death, comorbidities, elevations in serum cardiac markers as compared with patients without myocardial involvement. Otherwise, there was a significantly higher need for oxygen-support and a higher prevalence of cardiac disease in the myocarditis group. Patients with suspected myocarditis were older, had a higher frequency of previous cardiac disease, and significantly more prolonged hospitalization and a lower value of interleukin-6 than other COVID-19 patients. Further studies, specifically designed on this issue, are warranted.

Palliative care in a COVID-19 Internal Medicine ward: A preliminary report.

BACKGROUND: in the current pandemic emergency, increased attention has given to treating symptoms that cause suffering in patients with COVID-19. This study aims to describe the role of palliative care in the management of these patients. METHODS: palliative consultation was requested by the staff as per protocol. In brief, the criteria for referring patients to a palliative care physician or to undergo palliative care were left to the discretion of the physician in charge. We recorded data regarding age, gender, length of stay, type of discharge (dead or alive, and transfer to long-term or hospice facilities). RESULTS: Between March 18 to May 8, 2020, 412 patients with COVID-19 were admitted to the Internal Medicine wards of Magenta Hospital, Italy. The palliative care physician was directly involved in 105 cases (25.5%) and performed 236 consultations. Of the 105 patients who received palliative care counselling, 66 (63%) died. The average number of days in care was 2.26 days. The principal reason for counseling was controlling symptoms (54%) and 12% deal with the end of life management. The prevalent symptom, among those which led to the counseling, was restlessness/agitation (41%), followed by emotional issues (26%) such as anxiety, fear, and demoralization. In only 20% of cases, dyspnoea was the reason for symptomatic treatment. CONCLUSIONS: A large number of hospitalized Covid-19 patients are at high risk of clinical deterioration and death. This leads to the opportunity to integrate a palliative physician into the staff, who treat these patients. There is an urgent need for protocol standardization and formal trials to verify the effectiveness of this approach.

Anti-IL6 treatment of serious COVID-19 disease: A monocentric retrospective experience.

ABSTRACT: COVID-19 is causing a high influx of patients suffering from serious respiratory complications leading the necessity to find effective therapies. These patients seem to present with cytokine perturbation and high levels of IL6. Tocilizumab and sarilumab could be effective in this condition.We retrospectively collected data about 112 consecutive hospitalized in a single center.Fifty (IL6 group) treated with tocilizumab (8 mg/kg intravenously [IV], 2 infusions 12 hours apart) or sarilumab 400 mg IV once and 62 treated with the standard of care but not anti-cytokine drugs (CONTROL group).To determine whether anti-IL6 drugs are effective in improving prognosis and reducing hospitalization times and mortality in COVID-19 pneumonia.To date 84% (42/50) of IL6 group patients have already been discharged and only 2/50 are still recovered and intubated in intensive care. Six/fifty patients (12%) died: 5/6 due to severe respiratory failure within a framework of severe acute respiratory distress syndrome (ARDS), 1 suffered an acute myocardial infarction, and 1 died of massive pulmonary thromboembolism. There were no adverse treatment events or infectious complications. Compared to the CONTROL group they showed a lower mortality rate (12% versus 43%), for the same number of complications and days of hospitalization.Anti-IL6 drugs seem to be effective in the treatment of medium to severe forms of COVID-19 pneumonia reducing the risk of mortality due to multi-organ failure, acting at the systemic level and reducing inflammation levels and therefore microvascular complications. However, it is essential to identify the best time for treatment, which, if delayed, is rendered useless as well as counterproductive. Further studies and ongoing clinical trials will help us to better define patients eligible as candidates for more aggressive intervention.

Clinical immunity in discharged medical patients with COVID-19.

BACKGROUND: Most studies on SARS-CoV-2 infection show that people who have recovered from COVID-19 have antibodies to the virus. No study has evaluated whether the presence of antibodies to SARS-CoV-2 confers immunity to the infection relapse but however, to date, no human reinfections with SARS-CoV-2 have been confirmed. MATERIAL AND METHODS: In our prospective, multicenter, cohort study we investigated within three months all patients, with confirmed COVID-19, discharged from two Hospitals (Legnano and Magenta Hospitals), in an area of Italy severely affected by the infection. Telephone follow-up at 1 and 2 months and clinical contact within 3 months was initiated; demographic, clinical, radiologic and laboratory data were recorded in electronic medical records and updated. RESULTS: Of 1081 patients involved, 804 (74.3%) were discharged alive. For all these patients we obtained follow-up data. At 1 and 2 months none has died and none has had any signs of recurrence of infectious at both telephone interview and clinical visit. CONCLUSION: Our clinical observation have confirmed two basic points: the reinfection is very unlikely and any antibody immunity protects against recurrence, at least in the short term.