COVID-19 in B Cell-Depleted Patients After Rituximab: A Diagnostic and Therapeutic Challenge.

B cell-targeting strategies such as rituximab are widely used in B cell hematologic malignancies, rheumatologic and musculoskeletal diseases and a variety of autoimmune disorders. The purpose of this paper is to illustrate how exposure to anti-CD20 treatment profoundly affects B cell functions involved in anti-SARS-CoV-2 immunity and significantly impacts on the clinical and serological course of SARS-CoV-2 infection, long term immunity and vaccine responses. The data presented here suggest that the effects of B cell-depleting agents on adaptive immunity should be taken into account for the proper selection and interpretation of SARS-CoV-2 diagnostics and to guide appropriate therapeutic approaches and protective measures. Combination therapeutic strategies including immunotherapy in association with prolonged antiviral treatment may play a decisive role in the setting of B cell immune deficiencies.

Chest radiography findings of COVID-19 pneumonia: a specific pattern for a confident differential diagnosis.

BACKGROUND: Chest radiography (CR) patterns for the diagnosis of COVID-19 have been established. However, they were not ideated comparing CR features with those of other pulmonary diseases. PURPOSE: To create the most accurate COVID-19 pneumonia pattern comparing CR findings of COVID-19 and non-COVID-19 pulmonary diseases and to test the model against the British Society of Thoracic Imaging (BSTI) criteria. MATERIAL AND METHODS: CR of COVID-19 and non-COVID-19 pulmonary diseases, admitted to the emergency department, were evaluated. Assessed features were interstitial opacities, ground glass opacities, and/or consolidations and the predominant lung alteration. We also assessed uni-/bilaterality, location (upper/middle/lower), and distribution (peripheral/perihilar), as well as pleural effusion and perihilar vessels blurring. A binary logistic regression was adopted to obtain the most accurate CR COVID-19 pattern, and sensitivity and specificity were computed. The newly defined pattern was compared to BSTI criteria. RESULTS: CR of 274 patients were evaluated (146 COVID-19, 128 non-COVID-19). The most accurate COVID-19 pneumonia pattern consisted of four features: bilateral alterations (Expß=2.8, P=0.002), peripheral distribution of the predominant (Expß=2.3, P=0.013), no pleural effusion (Expß=0.4, P=0.009), and perihilar vessels' contour not blurred (Expß=0.3, P=0.002). The pattern showed 49% sensitivity, 81% specificity, and 64% accuracy, while BSTI criteria showed 51%, 77%, and 63%, respectively. CONCLUSION: Bilaterality, peripheral distribution of the predominant lung alteration, no pleural effusion, and perihilar vessels contour not blurred determine the most accurate COVID-19 pneumonia pattern. Lower field involvement, proposed by BSTI criteria, was not a distinctive finding. The BSTI criteria has lower specificity.

A Severe Acute Respiratory Syndrome Coronavirus 2 detection method based on nasal and nasopharyngeal lavage fluid: A pilot feasibility study.

OBJECTIVE: Nose and nasopharyngeal swab is the preferred and worldwide-accepted method to detect the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) within the nose and nasopharynx. This method may be linked with possible difficulties, such as patient's discomfort or complications. This article shows a pilot study of SARS-CoV-2 detection with nasal and nasopharyngeal lavage fluids (level of evidence: 3). METHODS: Nasal lavage fluid was collected from patients who were submitted to SARS-CoV-2 screening test, due to a preceding positive rapid antigen test. A control group was enrolled among health care professionals whose nasopharyngeal swab tested negative. Nasal lavages were performed using isotonic saline solution injected through a nasal fossa. Both lavage fluid and traditional nasopharyngeal swab were analyzed by real-time (RT) PCR and antigenic test. RESULTS: A total of 49 positive subjects were enrolled in the study. Results of the analysis on lavages and nasopharyngeal swabs were concordant for 48 cases, regardless of the antigenic and molecular test performed. RT-PCR resulted weakly positive at swab in one case and negative at lavage fluid. Among the control group (44 subjects), nasopharyngeal swab and lavage fluid analyses returned a negative result. Sensitivity of the molecular test based on nasal lavage fluid, compared to traditional nasal swab, was 97.7%, specificity was 100%, and accuracy was 98.9%, with high agreement (Cohen's κ, 0.978). CONCLUSION: Nasal and nasopharyngeal lavages resulted to be highly reliable and well tolerated. A larger series is needed to confirm these results. This approach may potentially represent a valid alternative to the traditional swab method in selected cases. LEVEL OF EVIDENCE: 3.

Community Use of Face Masks against the Spread of COVID-19.

The role of face masks to prevent and control COVID-19 is critical, especially since asymptomatic or pre-symptomatic infected individuals can shed high loads of SARS-CoV-2 in the surrounding environment. In addition to being a two-way barrier to protect against virions droplets both in terms of "source control" (for the benefits of the community) and "physical protection" (for wearer), face masks also allow maintaining physiological temperatures and humidity of the nasal cavity and mouth, independently from the external environmental conditions. Beyond compromising the viral transmission speed, exposure to cold environments could have a detrimental effect on the host's susceptibility to SARS-CoV-2. The innate human immune system becomes in fact weaker with cooler nose temperatures and thus more vulnerable to viral replication. Furthermore, there is evidence that warm, humid climates are associated with reduced spread of SARS-CoV-2, while cold dry conditions favor its stability and transmissibility. In the early stage of a viral infection, a physiological body temperature in the upper airways supports the innate immune system, endorsing the muco-ciliary clearance, inhibiting, or deactivating any first settlement of viruses. Face masks are therefore strongly recommended also outdoors, especially under cold weather conditions, not only as a physical barrier against the transmission of SARS-CoV-2, but also to prevent the rapid cooling of the nasal mucosa and the inhibition of the human innate defense of the upper airways.

Six-Month Psychophysical Evaluation of Olfactory Dysfunction in Patients with COVID-19.

This study prospectively assessed the 6-month prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 10 patients being anosmic (6.9%) and seven being severely microsmic (4.8%). At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of the sense of smell or taste and olfactory test scores (Spearman's r = -0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had a self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of syndrome coronavirus 2 (SARS-CoV-2) infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-COV-2 infection.

Suppression of Covid-19 outbreak among healthcare workers at the Treviso Regional Hospital, Italy and lessons for ophthalmologists.

PURPOSE: To describe a strategy to reduce Covid-19 spread among healthcare workers and provide ophthalmologists with recommendations useful for a possible second wave of Covid-19 in Autumn. METHODS: Epidemiological surveillance at the Cà Foncello Hospital (Veneto, Italy) since 24 February 2020 to 24 April 2020 when the municipality of Treviso was hit by the Covid-19 outbreak. The number of naso-pharigeal (NP) swabs performed was 7010. RESULTS: The number of infected among healthcare workers was 209/ 3924 (5.32%): medical doctors: 28 cases / 498 (5.6%). None among ophthalmologists; specialized nurses: 86/1294 (6.4%) None in the ophthalmic unit; intermediate care technicians: 68/463 (14.7%). The 46% of the positive tested were asymptomatic. We share key suggested actions for the reorganization in ophthalmological services: be part of a global epidemiological local strategy of containment (Testing, Tracing, Treating); protect your department: Keep on screening patients by telephone interview before entering the hospital; promote continuous and appropriate use of PPE both for doctors and for patients; make any effort to obtain a continuous flow of patients in every line of the ophthalmic service; treat appropriately any single patient with vision threatening condition; avoid unnecessary or futile testings and examinations. CONCLUSION: The Treviso model shows that it is possible and safe to keep on performing high risk hospital activities like ophthalmology, even in the epicenter of covid outbreak, if adequate actions are performed. We discuss about the value of NP swabs and serological tests as a strategy in case of a second wave of infections.

Evolution of Altered Sense of Smell or Taste in Patients With Mildly Symptomatic COVID-19.

Importance: An altered sense of smell and taste has been reported to be associated with coronavirus disease 2019 (COVID-19). To understand the evolution of these symptoms during the course of the disease is important to identify patients with persistent loss of smell or taste and estimate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the burden of olfactory and gustative dysfunctions. Objective: To evaluate the evolution of the loss of sense of smell and taste in a case series of mildly symptomatic patients with SARS-CoV-2 infection. Design, Setting, and Participants: This cross-sectional survey-based study included 202 mildly symptomatic adults (≥18 years) consecutively assessed at Treviso Regional Hospital, Italy, between March 19 and March 22, 2020, who tested positive for SARS-CoV-2 RNA by polymerase chain reaction on nasopharyngeal and throat swabs. Main Outcomes and Measures: Prevalence of altered sense of smell and taste at follow-up and their variation from baseline. Results: Of 202 patients completing the survey at baseline, 187 (92.6%) also completed the follow-up survey (103 [55.1%] women; median age, 56 years). The evaluation of the evolution of altered sense of smell or taste in the 113 patients reporting sudden onset of these symptoms at baseline showed that 55 patients (48.7%; 95% CI, 39.2-58.3) reported complete resolution of smell or taste impairment, 46 (40.7%; 95% CI, 31.6-50.4) reported an improvement in the severity, and only 12 (10.6%; 95% CI, 5.6-17.8) reported the symptom was unchanged or worse. Persistent loss of smell or taste was not associated with persistent SARS-CoV-2 infection. Conclusions and Relevance: At 4 weeks from the onset, 89% of the SARS-CoV-2-positive mildly symptomatic patients who had had a sudden onset of altered sense of smell or taste experienced a complete resolution or improvement of these symptoms. Persistent loss of smell or taste was not associated with persistent SARS-CoV-2 infection.

Use of RAAS Inhibitors and Risk of Clinical Deterioration in COVID-19: Results From an Italian Cohort of 133 Hypertensives.

BACKGROUND: The effect of chronic use of renin-angiotensin-aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19-related outcomes in hypertensive patients. METHODS: A single-center study was conducted on 133 consecutive hypertensive subjects presenting to the emergency department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9 and 31 March 2020. RESULTS: All patients were grouped according to their chronic antihypertensive medications (ACEIs, N = 40; ARBs, N = 42; not on RAAS inhibitors, N = 51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy, and need for noninvasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared with the non-RAAS population (odds ratio (OR) 0.25, confidence interval (CI) 95% 0.09-0.66, P = 0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI 95% 0.17-1.83, P = 0.341). CONCLUSIONS: Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID-19-related morbidity and mortality.

New onset of loss of smell or taste in household contacts of home-isolated SARS-CoV-2-positive subjects.

PURPOSE: To estimate the prevalence of smell or taste impairment in household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. METHODS: Cross-sectional study based on ad hoc questions. RESULTS: Of 214 mildly symptomatic COVID-19 patients managed at home under self-isolation, 179 reported to have at least one household contact, with the total number of no study participants contacts being 296. Among 175 household contacts not tested for SARS-CoV-2 infection, 67 (38.3%) had SARS-CoV-2 compatible symptoms, 39 (22.3%) had loss of smell or taste with 7 (4.0%) having loss of smell or taste in the absence of other symptoms. The prevalence of smell or taste impairment was 1.5% in patients tested negative compared to 63.0% of those tested positive for SARS-CoV-2 (p < 0.001). CONCLUSION: Smell or taste impairment are quite common in not-tested household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. This should be taken into account when estimating the burden of loss of sense of smell and taste during COVID-19 pandemic, and further highlights the value of loss of sense of smell and taste as a marker of infection.