The Impact of Routine Molecular Screening for SARS-CoV-2 in Patients Receiving Anticancer Therapy: An Interim Analysis of the Observational COICA Study.

Introduction: Cancer aggravates COVID-19 prognosis. Nosocomial transmission of SARS-CoV-2 is particularly frequent in cancer patients, who need to attend hospitals regularly. Since March 2020, all cancer patients having access to the Oncology Unit at the "Andrea Tortora" Hospital (Pagani, Salerno - referred to as "the Hospital") as inpatients or outpatients receiving intravenous therapy have been screened for SARS-CoV-2 using RT-PCR nasal swab. The ongoing COICA (COVID-19 infection in cancer patients) study is an ambispective, multicenter, observational study designed to assess the prognosis of SARS-CoV-2 infection in cancer patients. The aim of the study presented here was to explore potential differences in COVID-19-related outcomes among screening-detected versus nonscreening-detected SARS-CoV-2-infected patients. Methods: The COICA study enrolled cancer patients who had received any anticancer systemic therapy within 3 months since the day they tested positive for SARS-CoV-2 on RT-PCR. The target accrual is 128 patients, and the study was approved by the competent Ethics Committee. Only the subgroup of patients enrolled at the Hospital was considered in this unplanned interim analysis. Logistic regression analysis was used to evaluate the association of screening-based versus nonscreening-based diagnosis. Results: Since March 15, 2020, until August 15, 2021, a total of 931 outpatients and 230 inpatients were repeatedly screened for SARS-CoV-2 using RT-PCR nasal swab at the Hospital. Among these, 71 asymptomatic patients were positive on routine screening and 5 patients were positive for SARS-CoV-2 outside the institutional screening. Seven patients died because of COVID-19. At univariate analysis, nonscreening- versus screening-detected SARS-CoV-2 infection was associated with significantly higher odds of O2 therapy (OR = 16.2; 95% CI = 2.2-117.1; p = 0.006), hospital admission (OR = 31.5; 95% CI = 3.1-317.8; p = 0.003), admission to ICU (OR = 23.0; 95% CI = 2.4-223.8; p = 0.007), and death (OR = 8.8; 95% CI = 1.2-65.5; p = 0.034). Conclusion: Routine screening with RT-PCR may represent a feasible and effective strategy in reducing viral circulation and possibly COVID-19 mortality in patients with active cancer having repeated access to hospital facilities.

The Effect of Vaccination against COVID-19 in Cancer Patients: Final Results of the COICA Trial.

Background: The COICA study is an ambispective, observational trial that was conceived to assess the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in cancer patients. A recently published, population-based, case-control study reported a reduced vaccine efficacy at 3-6 months in cancer patients compared to individuals without cancer. Objectives: The aim of the study was to describe coronavirus disease 19 (COVID-19) outcomes in cancer patients and analyze differences in SARS-CoV-2 outcomes between vaccinated and unvaccinated patients. Methods: Descriptive statistics and frequency counts were used to summarize characteristics of the study population. χ2 test and the log-rank test were used to compare outcomes between vaccinated and unvaccinated patients. Results: A total of 141 cancer patients (80 males, 61 females) were recruited at two participating Institutions from March 2020 until April 2022 and observed from the time of positive SARS-CoV-2 test to the time of negativization or death. Approximately 35% of patients had been vaccinated at the time of infection with 2 (16 patients) or 3 (33 patients) vaccine doses. Vaccinated patients consistently and significantly showed improved COVID-19 outcomes compared to unvaccinated patients, with CT-diagnosed pneumonia, hospitalization, O2 therapy, and death reported in 0% versus 48.6%, 2.0% versus 15.2%, 0% versus 14.1%, and 0% versus 7.6%, respectively, of assessable patients (p < 0.05). Vaccinated versus unvaccinated patients showed a significantly shorter time to negativization, with a median (95% confidence interval) time of 12 (10-14) versus 20 (17-23) days, respectively (p < 0.001). Conclusions: Vaccination consistently improved all COVID-19 outcomes. No death was recorded among vaccinated patients. Additional research is especially warranted to establish optimal timing and patient selection for administration of the fourth vaccination dose.

Germline rare variants of lectin pathway genes predispose to asymptomatic SARS-CoV-2 infection in elderly individuals.

PURPOSE: Emerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants - referred as qualifying variants (QVs) - of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease. METHODS: Exploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19. RESULTS: We found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue. CONCLUSION: This study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/.

Assessment of Saliva Specimens' Reliability for COVID-19 Surveillance.

The aim of the present study is to assess saliva as a reliable specimen for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse transcription-PCR (RT-PCR), especially in community mass screening programs. The performance analysis considered 1,221 total samples [nasopharyngeal (NP) swabs and corresponding saliva], tested by means of a reference diagnostic real-time RT-PCR assay. Conflicting results were further investigated with a second, more sensitive, reference assay. Analysis of agreement showed a good concordance (95.82%), with a k coefficient value of.74 (p < 0.001); moreover, a follow-up analysis revealed the presence of viral gene targets in saliva samples at the time point the corresponding NP swabs turned negative. Data obtained prove the reliability of this alternative biofluid for SARS-CoV-2 detection in real-time RT-PCR. Considering the role of saliva in the coronavirus disease 2019 (COVID-19) transmission and pathogenesis, and the advantages in the use of salivary diagnostics, the present validation supports the use of saliva as an optimal choice in large-scale population screening and monitoring of the SARS-CoV-2 virus.

Durability of Humoral Immune Responses to SARS-CoV-2 in Citizens of Ariano Irpino (Campania, Italy): A Longitudinal Observational Study With an 11.5-Month Follow-Up.

As of November 17, 2021, SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2), the causative agent of COVID-19 (COronaVIrus Disease 19), has infected ~250 million people worldwide, causing around five million deaths. Titers of anti-SARS-CoV-2 neutralizing antibodies were relatively stable for at least 9 months in a population-based study conducted in Wuhan, China, both in symptomatic and in asymptomatic individuals. In the mass screening campaign conducted in the town of Ariano Irpino (Avellino, Italy) in May, 2020, 5.7% (95% CI: 5.3-6-1) of the 13,444 asymptomatic citizens screened were positive for anti-nucleocapsid antibodies against SARS-CoV-2. Among these, 422 citizens were re-tested for anti SARS-CoV-2 antibodies in January, 2021 and/or in April, 2021 and enrolled in this longitudinal observational study. Median (interquartile range) age of the study cohort was 46 years (29-59), with 47 (11.1%) participants of minor age, while 217 (51.4%) participants were females. There was no evidence of re-infection in any of the subjects included. Presence of anti-nuclear antibodies antibodies (Elecysis, Roche) was reported in 95.7 and 93.7% of evaluable participants in January and April, 2021. Multiple logistic regression analysis used to explore associations between age, sex and seroprevalence showed that adults vs. minors had significantly lower odds of having anti-S1 antibodies (Biorad) both in January, 2021 and in April, 2021. Our findings showed that antibodies remained detectable at least 11.5 months after infection in >90% of never symptomatic cases. Further investigation is required to establish duration of immunity against SARS-CoV-2.

No detection of SARS-CoV-2 in animals exposed to infected keepers: results of a COVID-19 surveillance program.

SARS-CoV-2, the causative agent of the COVID-19 pandemic, has rarely been associated with transmission from humans to animals (reverse zoonotic transmission). In this retrospective study, the authors reviewed data obtained from 236 animals, including buffaloes, goats/sheep, horses, carrier pigeons, rabbits, hens, snakes, pigs and cows that were screened for SARS-CoV-2 infection because they had been in contact with their SARS-CoV-2-positive breeder for at least 2 weeks. None of the tested animals were found to be positive. The authors' findings suggest that the risk of reverse zoonotic transmission among bred animals and SARS-CoV-2-positive breeders is very low or nonexistent. Additional studies are warranted.

An observational study of a cohort of citizens receiving the AZD1222 vaccine against SARS-CoV-2.

In this retrospective study, a cohort of 67 subjects vaccinated with AZD1222 was retrospectively observed. Consistently with published findings, no serious adverse event was reported, and all adverse events reported (fever, muscle ache and/or pain in the site of injection) had resolved by day 8. Of note, some citizens were prescribed low-dose aspirin and even heparin for thrombosis prevention. We also found variations in laboratory test results (full blood count and chemistry) on day 1 compared with day 8. Physicians should be aware that no prevention therapy for thrombosis is currently recommended, given the very low incidence of this side effect. Additional studies are warranted to interpret our findings.

The TNFRSF13C H159Y Variant Is Associated with Severe COVID-19: A Retrospective Study of 500 Patients from Southern Italy.

To identify host genetic determinants involved in humoral immunity and associated with the risk of developing severe COVID-19, we analyzed 500 SARS-CoV-2 positive subjects from Southern Italy. We examined the coding sequences of 10 common variable immunodeficiency-associated genes obtained by the whole-exome sequencing of 121 hospitalized patients. These 10 genes showed significant enrichment in predicted pathogenic point mutations in severe patients compared with the non-severe ones. Moreover, in the TNFRSF13C gene, the minor allele of the p.His159Tyr variant, which is known to increase NF-kB activation and B-cell production, was significantly more frequent in the 38 severe cases compared to both the 83 non-severe patients and the 375 asymptomatic subjects further genotyped. This finding identified a potential genetic risk factor of severe COVID-19 that not only may serve to unravel the mechanisms underlying the disease severity but, also, may contribute to build the rationale for individualized management based on B-cell therapy.

Regulatory Noncoding and Predicted Pathogenic Coding Variants of CCR5 Predispose to Severe COVID-19.

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10-5) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.

Seroprevalence of SARS-CoV-2 Assessed by Four Chemiluminescence Immunoassays and One Immunocromatography Test for SARS-Cov-2.

The onset of the new SARS-CoV-2 coronavirus encouraged the development of new serologic tests that could be additional and complementary to real-time RT-PCR-based assays. In such a context, the study of performances of available tests is urgently needed, as their use has just been initiated for seroprevalence assessment. The aim of this study was to compare four chemiluminescence immunoassays and one immunochromatography test for SARS-Cov-2 antibodies for the evaluation of the degree of diffusion of SARS-CoV-2 infection in Salerno Province (Campania Region, Italy). A total of 3,185 specimens from citizens were tested for anti-SARS-CoV-2 antibodies as part of a screening program. Four automated immunoassays (Abbott and Liaison SARS-CoV-2 CLIA IgG and Roche and Siemens SARS-CoV-2 CLIA IgM/IgG/IgA assays) and one lateral flow immunoassay (LFIA Technogenetics IgG-IgM COVID-19) were used. Seroprevalence in the entire cohort was 2.41, 2.10, 1.82, and 1.85% according to the Liaison IgG, Abbott IgG, Siemens, and Roche total Ig tests, respectively. When we explored the agreement among the rapid tests and the serologic assays, we reported good agreement for Abbott, Siemens, and Roche (Cohen's Kappa coefficient 0.69, 0.67, and 0.67, respectively), whereas we found moderate agreement for Liaison (Cohen's kappa coefficient 0.58). Our study showed that Abbott and Liaison SARS-CoV-2 CLIA IgG, Roche and Siemens SARS-CoV-2 CLIA IgM/IgG/IgA assays, and LFIA Technogenetics IgG-IgM COVID-19 have good agreement in seroprevalence assessment. In addition, our findings indicate that the prevalence of IgG and total Ig antibodies against SARS-CoV-2 at the time of the study was as low as around 3%, likely explaining the amplitude of the current second wave.

Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19.

The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex, and comorbidities, but they do not fully explain the wide spectrum of disease manifestations. Genetic factors implicated in the host antiviral response provide for novel insights into its pathogenesis. We performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data, including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 and near MX1 gene show associations with severe COVID-19. The minor alleles of the five single nucleotide polymorphisms (SNPs) correlated with a reduced risk of developing severe COVID-19 and high level of MX1 expression in blood. Our findings demonstrate that host genetic factors can influence the different clinical presentations of COVID-19 and that MX1 could be a potential therapeutic target.

Seroprevalence of SARS-CoV-2-specific antibodies in the town of Ariano Irpino (Avellino, Campania, Italy): a population-based study.

The Italian municipality of Ariano Irpino (Avellino, Campania, Italy) was locked down by the regional authorities from March until April 2020 after several citizens tested positive for SARS coronavirus 2 (SARS-CoV-2). A serological mass screening campaign targeting the Ariano Irpino population using the Roche Cobas Elecsys anti-SARS-CoV-2 assay was organized by the Zoo-Prophylactic Institute of Southern Italy (Portici, Italy) and conducted in cooperation with the Local Health Unit (Azienda Sanitaria Locale - ASL - Avellino, Avellino, Italy), the Department of Public Health of University Federico II (Naples, Italy) and Department of Health Services of Azienda Ospedaliera dei Colli-Cotugno and Monaldi Hospital (Naples, Italy) in May 2020. A total of 13,218 asymptomatic individuals were reviewed in this analysis. A total of 738 citizens tested positive for anti-SARS-CoV-2 antibodies (398 females, 340 males). The overall prevalence in the sample was 5.6% (95% CI: 5.2-6.0). Among seropositive citizens, 101 cases tested positive on RT-PCR (0.76% of the overall population). Among citizens aged 14-18, 18-65 and >65 years, the seroprevalence was equal to 6.1 (95% CI: 4.1-8.7), 5.6 (95% CI: 5.1-6.1) and 4% (95% CI: 3.3-4.8), respectively. In the pediatric cohort (<14 years old), seroprevalence was 13% (95% CI: 10.2-16.2). A serological-based screening strategy could be a cost-effective public health intervention to tackle the COVID-19 pandemic.

The use of chest ultrasonography in suspected cases of COVID-19 in the emergency department.

AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-specific reverse transcriptase-polymerase chain reaction (RT-PCR) represents the diagnostic gold standard. We explored the value of chest ultrasonography to predict positivity to SARS-CoV-2 on RT-PCR in suspected COVID-19 cases. PATIENTS & METHODS: Consecutive patients with suspect COVID-19 were included if they had fever and/or history of cough and/or dyspnea. Lung ultrasound score (LUSS) was computed according to published methods. RESULTS: A total of 76 patients were included. A 3-variable model based on aspartate transaminase (AST) > upper limit of normal, LUSS >12 and body temperature >37.5°C yielded an overall accuracy of 91%. CONCLUSION: A simple LUSS-based model may represent a powerful tool for initial assessment in suspected cases of COVID-19.

Perspective: Cancer Patient Management Challenges During the COVID-19 Pandemic.

On March 11, 2020, the WHO has declared the coronavirus disease 2019 (COVID-19) a global pandemic. As the last few months have profoundly changed the delivery of health care in the world, we should recognize the effort of numerous comprehensive cancer centers to share experiences and knowledge to develop best practices to care for oncological patients during the COVID-19 pandemic. Patients as well as physicians must be aware of all these constraints and profound social, personal, and medical challenges posed by the tackling of this deadly disease in everyday life in order to adjust to such a completely novel scenario. This review will discuss facing the challenges and the current approaches that cancer centers in Italy and United States are adopting in order to cope with clinical and research activities.

Clinical Characteristics of Metastatic Prostate Cancer Patients Infected with COVID-19 in South Italy.

BACKGROUND: To date, the clinical characteristics of coronavirus disease 19 (COVID-19)-infected urologic cancer patients are unknown. METHODS: We have analyzed all patients with prostate cancer undergoing hormonal or chemotherapy treatment and receiving telephone and in person pre-triage between March 1 and 27, 2020, at the Tortora Hospital, Pagani, Italy. RESULTS: Among 72 patients, 48 and 24 were hormone-sensitive (HS) and castration-resistant prostate cancer (CRPC), respectively; 0 HS and 2 (8.3%) CRPC (p < 0.05) were positive for COVID-19. Both patients were receiving LHRH agonist therapy, and 1 patient was receiving enzalutamide. Urgent intensive care unit admission was required due to clinical worsening. Blood tests showed severe lymphopenia, anemia, and an increase in platelets. Retroviral therapy, antibiotics, heparin, and chloroquine were prescribed at the beginning. One patient also received tocilizumab as a salvage treatment. After 3 weeks of hospitalization, the patients were discharged from the hospital. Both patients suffered from an aggressive COVID-19 course due to concomitant comorbidities. CONCLUSIONS: Investigating whether hormonal therapy, especially in advanced disease, acts as a protective factor or a risk factor during COVID-19 could be useful.