The Impact of SARS-CoV-2 Infection in Patients with Inborn Errors of Immunity: the Experience of the Italian Primary Immunodeficiencies Network (IPINet).

COVID-19 manifestations range from asymptomatic to life-threatening infections. The outcome in different inborn errors of immunity (IEI) is still a matter of debate. In this retrospective study, we describe the experience of the of the Italian Primary Immunodeficiencies Network (IPINet). Sixteen reference centers for adult or pediatric IEI were involved. One hundred fourteen patients were enrolled including 35 pediatric and 79 adult patients. Median age was 32 years, and male-to-female ratio was 1.5:1. The most common IEI were 22q11.2 deletion syndrome in children (26%) and common variable immunodeficiency (CVID) in adults (65%). Ninety-one patients did not require hospital admission, and among these, 33 were asymptomatic. Hospitalization rate was 20.17%. Older age (p 0.004) and chronic lung disease (p 0.0008) represented risk factors for hospitalization. Hospitalized patients mainly included adults suffering from humoral immunodeficiencies requiring immunoglobulin replacement therapy and as expected had lower B cell counts compared to non-hospitalized patients. Infection fatality rate in the whole cohort was 3.5%. Seroconversion was observed is 86.6% of the patients evaluated and in 83.3% of CVID patients. 16.85% of the patients reported long-lasting COVID symptoms. All but one patient with prolonged symptoms were under IgRT. The fatality rate observed in IEI was slightly similar to the general population. The age of the patients who did not survive was lower compared to the general population, and the age stratified mortality in the 50-60 age range considerable exceeded the mortality from 50 to 60 age group of the Italian population (14.3 vs 0.6%; p < 0.0001). We hypothesize that this is due to the fact that comorbidities in IEI patients are very common and usually appear early in life.

Impact of Hypogammaglobulinemia on the Course of COVID-19 in a Non-Intensive Care Setting: A Single-Center Retrospective Cohort Study.

Background: Severity and mortality of COVID-19 largely depends on the ability of the immune system to clear the virus. Among various comorbidities potentially impacting on this process, the weight and the consequences of an antibody deficiency have not yet been clarified. Methods: We used serum protein electrophoresis to screen for hypogammaglobulinemia in a cohort of consecutive adult patients with COVID-19 pneumonia, hospitalized in non-intensive care setting between December 2020 and January 2021. The disease severity, measured by a validated score and by the need for semi intensive (sICU) or intensive care unit (ICU) admission, and the 30-day mortality was compared between patients presenting hypogammaglobulinemia (HYPO) and without hypogammaglobulinemia (no-HYPO). Demographics, comorbidities, COVID-19 specific treatment during the hospital stay, disease duration, complications and laboratory parameters were also evaluated in both groups. Results: We enrolled 374 patients, of which 39 represented the HYPO cohort (10.4%). In 10/39 the condition was previously neglected, while in the other 29/39 hematologic malignancies were common (61.5%); 2/39 were on regular immunoglobulin replacement therapy (IgRT). Patients belonging to the HYPO group more frequently developed a severe COVID-19 and more often required sICU/ICU admission than no-HYPO patients. IgRT were administered in 8/39 during hospitalization; none of them died or needed sICU/ICU. Among HYPO cohort, we observed a significantly higher prevalence of neoplastic affections, of active oncologic treatment and bronchiectasis, together with higher prevalence of viral and bacterial superinfections, mechanical ventilation, convalescent plasma and SARS-CoV-2 monoclonal antibodies administration during hospital stay, and longer disease duration. Multivariate logistic regression analysis and Cox proportional hazard regression confirmed the impact of hypogammaglobulinemia on the COVID-19 severity and the probability of sICU/ICU admission. The analysis of the mortality rate in the whole cohort showed no significant difference between HYPO and no-HYPO. Conclusions: Hypogammaglobulinemia, regardless of its cause, in COVID-19 patients hospitalized in a non-intensive care setting was associated to a more severe disease course and more frequent admission to s-ICU/ICU, particularly in absence of IgRT. Our findings emphasize the add-value of routine serum protein electrophoresis evaluation in patients admitted with COVID-19 to support clinicians in patient care and to consider IgRT initiation during hospitalization.

The Effect of Isotonic Saline Nasal Lavages in Improving Symptoms in SARS-CoV-2 Infection: A Case-Control Study.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mainly colonizes nasopharynx. In upper airways acute infections, e.g., the common cold, saline nasal irrigations have a significant efficacy in reducing symptoms. The present study aimed to test the efficacy of nasal lavages in upper airways symptoms of Coronavirus Disease 2019 (COVID-19). Methods: A series of consecutive adult subjects who tested positive for SARS-CoV-2 from December 2020 to February 2021 performed daily nasal lavages with saline solution (Lavonase®-Purling, Lugo di Romagna, Italy) for 12 days, starting on the day after the SARS-CoV-2 positive swab. A control group included a historical series of patients who were infected in February-March 2020 and who did not perform lavages. An ad hoc questionnaire regarding symptoms was administered to each subjects at base-line and 10 days after diagnosis (i.e., on the same day of the control swab) in both cases and controls. Results: A total of 140 subjects were enrolled. 68 participants in the treatment group and 72 in the control group were included. 90% of respondents declared the lavages were simple to use and 70% declared they were satisfied. Symptoms of blocked nose, runny nose, or sneezing decreased by an average of 24.7% after the treatment. Blocked nose and sneezing increased in the same period of time in the control group. Ears and eyes symptoms, anosmia/ageusia symptoms, and infection duration (10.53 days in the treatment group and 10.48 days in the control group) didn't vary significantly among the two groups. Conclusion: Nasal lavages resulted to significantly decrease nasal symptoms in newly diagnosed SARS-CoV-2 patients. These devices proved to be well-tolerated and easy to be used. Further studies on a larger number of subjects are needed in order to possibly confirm these preliminary results.

Comparison between Dexamethasone and Methylprednisolone Therapy in Patients with COVID-19 Pneumonia Admitted to Non-Intensive Medical Units.

(1) Background: Data on different steroid compounds for the treatment of hospitalized COVID-19 (coronavirus disease 2019) patients are still limited. The aim of this study was to compare COVID-19 patients admitted to non-intensive units and treated with methylprednisolone or dexamethasone. (2) Methods: This was a single-center retrospective study that included consecutive patients with COVID-19 hospitalized in medical wards during the second wave of the pandemic. Thirty-day mortality and the need for intensive or semi-intensive care were the main clinical outcomes analyzed in patients receiving methylprednisolone (60 mg/day) compared with dexamethasone (6 mg/day). Secondary outcomes included complication rates, length of hospital stay, and time to viral clearance. (3) Results: Two-hundred-forty-six patients were included in the analysis, 110 treated with dexamethasone and 136 with methylprednisolone. No statistically significant differences were found between the two groups of patients regarding 30-day mortality (OR 1.35, CI95% 0.71-2.56, p = 0.351) and the need for intensive or semi-intensive care (OR 1.94, CI95% 0.81-4.66, p = 0.136). The complication rates, length of hospital stay, and time to viral clearance did not significantly differ between the two groups. (4) Conclusions: In patients hospitalized for COVID-19 in non-intensive units, the choice of different steroid compounds, such as dexamethasone or methylprednisolone, did not affect the main clinical outcomes.

COVID-Q: Validation of the first COVID-19 questionnaire based on patient-rated symptom gravity.

OBJECTIVES: The aim of the present study was to develop and validate the CoronaVirus-Disease-2019 (COVID-19) Questionnaire (COVID-Q), a novel symptom questionnaire specific for COVID-19 patients, to provide a comprehensive evaluation that may be helpful for physicians, and evaluate the questionnaire's performance in identifying subjects at higher risk of testing positive. MATERIALS AND METHODS: Consecutive non-hospitalised adults who underwent nasopharyngeal-throat swab for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) detection at Treviso Hospital in March 2020, were enrolled. Subjects were divided into positive (cases) and negative (controls). All subjects answered the COVID-Q. Patients not able to answer COVID-Q because of clinical conditions were excluded. Parallel Analysis and Principal Component Analysis identified items measuring the same dimension. The Item Response Theory (IRT)-based analyses evaluated the functioning of item categories, the presence of clusters of local dependence among items, item fit within the model and model fit to the data. RESULTS: Answers obtained from 230 cases (113 males; mean age 55 years, range 20-99) and 230 controls (61 males; mean age 46 years, range 21-89) were analysed. Six components were extracted with parallel analysis: asthenia, influenza-like symptoms, ear and nose symptoms, breathing issues, throat symptoms, and anosmia/ageusia. The final IRT models retained 27 items as significant for symptom assessment. The total questionnaire's score was significantly associated with positivity to the molecular test: subjects with multiple symptoms were more likely to be affected (P < .001). Older age, male gender presence of breathing issues and anosmia/ageusia were significantly related to positivity (P < .001). Comorbidities had not a significant association with the COVID-19 diagnosis. CONCLUSION: COVID-Q could be validated since the evaluated aspects were overall significantly related to infection. The application of the questionnaire to clinical practice may help to identify subjects who are likely to be affected by COVID-19 and address them to a nasopharyngeal swab in order to achieve an early diagnosis.

Venom immunotherapy during COVID-19 pandemic: Experience from a University Allergy Center in Northern Italy.

During the ongoing pandemic of Coronavirus Disease 2019 (COVID-19) allergic patients need to continue their constant and proper treatment, including allergen-specific immunotherapy. These patients are expected to be at a higher risk for exacerbation of lung inflammation during viral infection. We investigated the putative interplay existing between allergen-specific immunotherapy and COVID-19 infection in a Hymenoptera venom-allergic population. We evaluated the frequency and severity of COVID-19 infection in a cohort of 211 subjects referring to our center for the regular administration of venom immunotherapy (VIT). Our result showed that the median age of our cohort is similar to the one that in our region has been associated with a high incidence of COVID-19 infection, increased hospitalization, and mortality rates. We reported only an isolated positivity of COVID-19 in the overall group; whereas none suffered from upper airway symptoms associated with COVID-19 (fever, cough, dyspnoea, sore throat, anosmia, and/or ageusia). Even though the demographic characteristics pose a substantial risk for such a population, we suggest that a regular administration of VIT may help in the development of an immunological milieu able to down modulate the Th1/Th17 environment that has been linked to inflammatory manifestations of COVID-19. To the best of our knowledge, this is the first description of the incidence of COVID-19 infection in Hymenoptera venom allergic patients treated with VIT, suggesting indirectly that venom immune tolerance-inducing treatment may be capable of reducing the aberrant inflammatory response induced by the virus in this specific population.

Coronavirus disease 2019 in patients with inborn errors of immunity: An international study.

BACKGROUND: There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense. OBJECTIVE: We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2. METHODS: An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI. RESULTS: We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died. CONCLUSIONS: This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.

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.