Monoclonal Antibodies and Antivirals against SARS-CoV-2 Reduce the Risk of Long COVID: A Retrospective Propensity Score-Matched Case-Control Study.

Long COVID is a complex condition affecting quality of life, with limited therapeutic options. We investigated the occurrence of long COVID in subjects receiving early therapy with monoclonal antibodies (mAbs) or antivirals to reduce the risk of COVID-19 progression. In this retrospective study we enrolled 737 adult patients (aged 65.16 ± 13.46; 361F), who experienced COVID-19 between January 2021 and March 2022. Antiviral or mAbs were administered to symptomatic patients who did not require oxygen therapy or hospital admission for SARS-CoV-2 infection, and who were at high risk of progression to severe disease, as identified by age > 65 years or the presence of comorbidities. Long COVID, defined as newly or persistent long-term symptoms 4 weeks after the onset of the acute illness, was reported in 204 cases (28%). Age (OR 1.03; p < 0.001), gender (OR 1.88; p < 0.001) and at least three comorbidities (OR 3.49; p = 0.049) were directly associated with long COVID; conversely, vaccination (OR 0.59; p = 0.005) and mAbs/antivirals (OR 0.44; p = 0.002) were independently associated with a reduced risk of long COVID. At a propensity-score-matched analysis, the mAbs/antivirals group had a significantly lower occurrence of long COVID in comparison with untreated controls (11% vs. 34%; p = 0.001). In conclusion, mAbs and antivirals administered against the progression of COVID-19 were associated with a reduced risk of long COVID.

The First Identification in Italy of SARS-CoV-2 Omicron BA.4 Harboring KSF141_del: A Genomic Comparison with Omicron Sub-Variants.

The rapid emergence and worldwide detection of the SARS-CoV-2 Omicron variant underscore the importance of robust genomic surveillance systems and prompt information sharing among global public health partners. The Omicron variant has rapidly replaced the Delta variant as a dominating SARS-CoV-2 variant because of natural selection, favoring the variant with higher infectivity and stronger vaccine breakthrough capability. The Omicron variant is also known as B.1.1.529. It has four sub-variants, indicated as BA.1, BA.2, BA.3 and BA.4. Among them, BA.1 is the currently prevailing sub-variant, and BA.2 has been found to be able to alarmingly re-infect patients initially infected by Omicron BA.1. The BA.3 sub-variant is a combination of mutations of BA.1 and BA.2, especially in the spike protein. Today, the BA.4 variant is emerging, which is herein described, and it was the first detected in Italy. Via bioinformatic analysis, we are reporting that the BA.4 that was identified harbors a new mutation, specifically a deletion in the ORF1ab gene, corresponding to KSF141_del in non-structural protein 1 (nsp1), a critical virulence factor able to suppress host translation. The bioinformatics comparison analysis with the other three sub-variants reveals that the deletion was not present before and was never reported until now. Therefore, we can speculate that Omicron BA.4 will become a new dominating "variant of concern" and may also break vaccine protection. Moreover, we show that other proteins are mutated in the BA.4. In particular, seven mutations are recognized in the nucleocapsid (N) protein, and the capability of five different types of rapid antigenic tests are used to identify it.

Validation of GeneFinder COVID-19 Ag Plus Rapid Test and Its Potential Utility to Slowing Infection Waves: A Single-Center Laboratory Evaluation Study.

Diagnostic laboratory tools are essential to keep everyone safe and track newly emerging variants; on the other hand, "filter" screening tests recognizing positivity are valuable tools to avoid hectic laboratory work that, besides COVID-19, are also part of the routine. Therefore, complementary assays, such as rapid antigen tests (RATs), are essential in controlling and monitoring virus spread within the community, especially in the asymptomatic population. A subset of nasopharyngeal swab specimens resulted in SARS-CoV-2 positive and investigated for genomic characterization were used for RAT validation. RATs were performed immediately after sampling, following the manufacturer's instructions (reading at 15 min). RT-PCRs were carried out within 24 h of specimens' collection. Out of 603 patients, 145 (24.05%) tested positive by RT-PCR and RAT and 451 (74.79%) tested negative by both methods; discordant results (RT-PCR+/RAT- or RT-PCR-/RAT+) were obtained in 7 patients (1.16%). RATs' overall specificity and sensitivity were 96.03% (95%CI: 91.55-98.53%) and 99.78% (95%CI: 98.77-99.99%), respectively, taking RT-PCR as the reference. Overall, RAT negative predictive value was 98.69% (95%CI 97.17-99.40%). The GeneFinder COVID-19 Ag Plus Rapid Test performed well as a screening test for early diagnosis of COVID-19, especially in asymptomatic subjects. The data suggested that patients with RT-PCR-proven COVID-19 testing negative by RAT are unlikely to be infectious. GeneFinder COVID-19 Ag Plus Rapid Test also works on variants of concern (VOC) delta and omicron BA.1 and BA.2.

Comparison of Allplex™2019-nCoV and TaqPath™COVID-19 Assays

The clinical presentation of COVID-19 is non-specific, and to improve and limit the spread of the SARS-CoV-2 virus, an accurate diagnosis with a robust method is needed. A total of 500 nasopharyngeal swab specimens were tested for SARS-CoV-2. Of these, 184 samples were found to be positive with Allplex™2019-nCoV Assay, which is fully automated. All the positive samples were retested with TaqPath™COVID-19 CE-IVD RT-PCR Kit (after this, referred to as TaqPath™COVID-19), semi-automated. The comparison of RT-qPCR for SARS-CoV-2 genes target points shows only one target point in common, the N gene. Therefore, the N gene was used to compare both assays. We noticed different Ct values between the tests. Therefore, samples were divided into four groups depending to the Ct value results: (1) Ct < 25, (2) Ct 25–30, (3) Ct 30–35, (4) Ct > 35. TaqPath™COVID-19 Kit reconfirmed the results obtained from Allplex™2019-nCoV Assay. In conclusion, both the Allplex™2019-nCoV assay and TaqPath™COVID-19 tests accurately confirm the diagnosis of SARS-CoV-2 infection. Even if TaqPath™COVID-19 has a semi-automated workflow, it does not introduce bias in the diagnostic screening of SARS-CoV-2, and it supports the indirect identification of variants of concern to undergo sequencing.

BA.1 Omicron Variant of SARS-CoV-2: First Case Reported in Calabria Region, Italy

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. Several variants of concern (VOCs) have been identified so far. Recently, the B.1.1.529 (Omicron) variant of SARS-CoV-2 spread rapidly worldwide. We describe the first case of the Omicron genetic lineage BA.1 in our region. The patient is a physician who traveled to Johannesburg (South Africa) and returned to Reggio Calabria (Italy). He underwent a SARS-CoV-2 screening before leaving—a required procedure where travelers present a negative PCR test one-day prior to departing. Three days after arriving in Italy, he started experiencing cold symptoms. Clinically, he was without fever or severe respiratory symptoms and reported suffering from a cold and sore throat. The nasopharyngeal swab specimen was tested by TaqPath COVID-19 RT-PCR and sequenced by Sanger sequencing, and next-generation sequencing (NGS) data were processed with their relative software. A peculiar drop-off of the S gene was obtained with TaqPath COVID-19 RT-PCR. S gene mutations indicative of the Omicron variant were obtained with both sequencing methods, pointing out 17 mutations in the 29 recognized by Sanger and the 28 recognized by NGS.

Vitamin D Serum Levels in Subjects Tested for SARS-CoV-2: What Are the Differences among Acute, Healed, and Negative COVID-19 Patients? A Multicenter Real-Practice Study.

Vitamin D might play a role in counteracting COVID-19, albeit strong evidence is still lacking in the literature. The present multicenter real-practice study aimed to evaluate the differences of 25(OH)D3 serum levels in adults tested for SARS-CoV-2 (acute COVID-19 patients, subjects healed from COVID-19, and non-infected ones) recruited over a 6-month period (March-September 2021). In a sample of 117 subjects, a statistically significant difference was found, with acute COVID-19 patients demonstrating the lowest levels of serum 25(OH)D3 (9.63 ± 8.70 ng/mL), significantly lower than values reported by no-COVID-19 patients (15.96 ± 5.99 ng/mL, p = 0.0091) and healed COVID-19 patients (11.52 ± 4.90 ng/mL, p > 0.05). Male gender across the three groups displayed unfluctuating 25(OH)D3 levels, hinting at an inability to ensure adequate levels of the active vitamin D3 form (1α,25(OH)2D3). As a secondary endpoint, we assessed the correlation between serum 25(OH)D3 levels and pro-inflammatory cytokine interleukin-6 (IL-6) in patients with extremely low serum 25(OH)D3 levels (<1 ng/mL) and in a subset supplemented with 1α,25(OH)2D3. Although patients with severe hypovitaminosis-D showed no significant increase in IL-6 levels, acute COVID-19 patients manifested high circulating IL-6 at admission (females = 127.64 ± 22.24 pg/mL, males = 139.28 ± 48.95 ng/mL) which dropped drastically after the administration of 1α,25(OH)2D3 (1.84 ± 0.77 pg/mL and 2.65 ± 0.92 ng/mL, respectively). Taken together, these findings suggest that an administration of 1α,25(OH)2D3 might be helpful for treating male patients with an acute COVID-19 infection. Further studies on rapid correction of vitamin D deficiency with fast acting metabolites are warranted in COVID-19 patients.

Neuron-specific enolase serum levels in COVID-19 are related to the severity of lung injury.

The multifunctional role of neuron-specific enolase (NSE) in lung diseases is well established. As the lungs are greatly affected in COVID-19, we evaluated serum NSE levels in COVID-19 patients with and without dyspnea. In this study, we evaluated both SARS-CoV-2-infected and uninfected patients aged >18 years who were referred to hospitals in Catanzaro, Italy from March 30 to July 30, 2020. Epidemiological, clinical, and radiological characteristics, treatment, and outcome data were recorded and reviewed by a trained team of physicians. In total, 323 patients (178 men, 55.1% and 145 women, 44.9%) were enrolled; of these, 128 were COVID-19 patients (39.6%) and 195 were control patients (60.4%). Westergren's method was used to determine erythroid sedimentation rate. A chemiluminescence assay was used for measurement of interleukin-6, procalcitonin, C-reactive protein, and NSE. We detected significantly higher NSE values (P<0.05) in COVID-19 patients than in controls. Interestingly, within the COVID-19 group, we also observed a further significant increase in dyspnea (Dyspnea Scale and Exercise score: 8.2 ± 0.8; scores ranging from 0 to 10, with higher numbers indicating very severe shortness of breath). These data provide the background for further investigations into the potential role of NSE as a clinical marker of COVID-19 progression.

SARS-CoV-2 Translocate from Nasopharyngeal to Bronchoalveolar Site: A Case Presentation

The nasopharyngeal swab is commonly used for the diagnosis of SARS-CoV-2 infection. Since the swab is performed in this site, of course, it cannot detect the presence of the virus in other tissue districts such as the lung, brain, or bowel. In the present case report, the nasopharyngeal swab was negative twice. From this, the patient discontinued antiviral therapy. Nasopharyngeal swabs were maintained negative until five days later, when we recorded a severe impairment of the patient"s clinical condition. At this time, the bronchoalveolar lavage was positive for SARS-CoV-2. The purpose of the case herein described is to suggest paying attention to the nasopharyngeal swab result. A negative detection in nasopharyngeal swab could not be indicative of COVID-19 recovery.