Estimate false-negative RT-PCR rates for SARS-CoV-2. A systematic review and meta-analysis.

BACKGROUND: Molecular-based tests used to identify symptomatic or asymptomatic patients infected by SARS-CoV-2 are characterized by high specificity but scarce sensitivity, generating false-negative results. We aimed to estimate, through a systematic review of the literature, the rate of RT-PCR false negatives at initial testing for COVID-19. METHODS: We systematically searched Pubmed, Embase and CENTRAL as well as a list of reference literature. We included observational studies that collected samples from respiratory tract to detect SARS-CoV-2 RNA using RT-PCR, reporting the number of false-negative subjects and the number of final patients with a COVID-19 diagnosis. Reported rates of false negatives were pooled in a meta-analysis as appropriate. We assessed the risk of bias of included studies and graded the quality of evidence according to the GRADE method. All information in this article is current up to February 2021. RESULTS: We included 32 studies, enrolling more than 18,000 patients infected by SARS-CoV-2. The overall false-negative rate was 0.12 (95%CI from 0.10 to 0.14) with very low certainty of evidence. The impact of misdiagnoses was estimated according to disease prevalence; a range between 2 and 58/1,000 subjects could be misdiagnosed with a disease prevalence of 10%, increasing to 290/1,000 misdiagnosed subjects with a disease prevalence of 50%. CONCLUSIONS: This systematic review showed that up to 58% of COVID-19 patients may have initial false-negative RT-PCR results, suggesting the need to implement a correct diagnostic strategy to correctly identify suspected cases, thereby reducing false-negative results and decreasing the disease burden among the population.

SARS-CoV-2 infection is not associated with the emergence of monoclonal gammopathies.

BACKGROUND: Upon infection activated plasma cells produce large quantities of antibodies which can lead to the emergence of a monoclonal component (MC), detectable by serum protein electrophoresis (SPEP). This study aims to investigate any correlation between SARS-CoV-2 infection and MC development and, if identified, whether it persists during follow-up. METHODS: SPEPs of 786 patients admitted to hospitals between March 01 2020 and March 31 2022 were evaluated. Positive (SARS-CoV-2+) and negative (SARS-CoV-2-) patients to nasopharyngeal swab for SARS-CoV-2 by RT-PCR were included. The persistence/new occurrence of MC was investigated for all patients during follow-up. Patient groups were compared by chi-square analysis. RESULTS: MC was identified in 12% of all patients admitted to hospital, of which 28.7% were SARS-CoV-2+. The most common immunoglobulin isotype in both groups was IgG-k. There was no correlation between MC development and SARS-CoV-2 infection (p = 0.173). Furthermore, the risk of MC persistence in SARS-CoV-2-negative patients was revealed to be higher than in the SARS-CoV-2+ at follow-up (HR = 0.591, p = 0.05). CONCLUSIONS: Our study suggests that the detection of MC during SARS-CoV-2 infection is most likely due to the hyperstimulation of the humoral immune system, as also occurs in other viral infections.

Evidence of SARS-CoV-2 reinfection: analysis of 35,000 subjects and overview of systematic reviews.

BACKGROUND: Reinfection by SARS-CoV-2 is a rare but possible event. We evaluated the prevalence of reinfections in the Province of Modena and performed an overview of systematic reviews to summarize the current knowledge. METHODS: We applied big data analysis and retrospectively analysed the results of oro- or naso-pharyngeal swab results tested for molecular research of viral RNA of SARS-CoV-2 between 1 January 2021 and 30 June 2021 at a single center. We selected individuals with samples sequence of positive, negative and then positive results. Between first and second positive result we considered a time interval of 90 days to be sure of a reinfection. We also performed a search for and evaluation of systematic reviews reporting SARS-CoV-2 reinfection rates. Main information was collected and the methodological quality of each review was assessed, according to A Measurement Tool to Assess systematic Reviews (AMSTAR). RESULTS: Initial positive results were revealed in more than 35,000 (20%) subjects; most (28%) were aged 30-49 years old. Reinfection was reported in 1,258 (3.5%); most (33%) were aged 30-49 years old. Reinfection rates according to vaccinated or non-vaccinated subjects were 0.6% vs 1.1% (p < 0.0001). Nine systematic reviews were identified and confirmed that SARS-CoV-2 reinfection rate is a rare event. AMSTAR revealed very low-moderate levels of quality among selected systematic reviews. CONCLUSIONS: There is a real, albeit rare risk of SARS-CoV-2 reinfection. Big data analysis enabled accurate estimates of the reinfection rates. Nevertheless, a standardized approach to identify and report reinfection cases should be developed.

Glycemic control predicts SARS-CoV-2 prognosis in diabetic subjects.

AIM: The coronavirus disease (COVID)-19 incidence was higher in diabetes mellitus (DM), although several differences should be considered on the basis of characteristics of cohorts evaluated. This study was designed to evaluate the prevalence and potential consequences of COVID-19 in a large diabetic population in Northern Italy. DESIGN: Observational, longitudinal, retrospective, clinical study. METHODS: Subjects with both type 1 and type 2 DM living in the Province of Modena and submitted to at least one SARS-CoV-2 swab between March 2020 and March 2021 were included. Data were extracted from the Hospital data warehouse. RESULTS: 9553 diabetic subjects were enrolled (age 68.8 ± 14.1 years, diabetes duration 11.0 ± 6.9 years, glycated hemoglobin 57.2 ± 16.2 mmol/mol). COVID-19 was detected in 2302 patients (24.1%) with a death rate of 8.9%. The mean age and diabetes duration were significantly lower in infected versus non-infected patients. SARS-CoV-2 infection was more frequent in youngest people, according to quartile of age and retirement pension age of 65 years. No differences were detected considering sex. Higher HbA1c was detected in infected compared to non-infected patient. Death was predicted by diabetes duration and HbA1c. ROC analyses for death risk showed significant threshold for diabetes duration (10.9 years) and age (74.4 years). CONCLUSION: In our cohort, SARS-CoV-2 infection correlates with age, diabetes duration and disease control. Diabetic patients with COVID-19 should be carefully followed when older than 74 years and with more than 10 years of DM duration.

Prognostic Relevance of Multi-Antigenic Myeloma-Specific T-Cell Assay in Patients with Monoclonal Gammopathies.

Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease (p < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients' HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies.