Correction: SARS-CoV-2 Mutations Responsible for Immune Evasion Leading to Breakthrough Infection.

[This corrects the article DOI: 10.7759/cureus.29544.].

SARS-CoV-2 Mutations Responsible for Immune Evasion Leading to Breakthrough Infection.

BACKGROUND AND OBJECTIVES: India had faced a devastating second outbreak of COVID-19 infection, in which a majority of the viral sequences were found to be of the B.1.617.2 lineage (Delta-variant). While India and the world focused on vaccination, reports of vaccine-immunity evasion by the virus, termed "breakthrough cases", emerged worldwide. Our study was focused on the primary objective to identify the mutations associated with breakthrough infections SARS-CoV-2. METHODS: In our study, we extracted the SARS-CoV-2 RNA (ribonucleic acid) from reverse transcription-polymerase chain reaction (RT-PCR) positive COVID-19 patients, and 150 random samples were sent for sequencing to the Centre for Cellular & Molecular Biology, Hyderabad. Whole genome sequences of 150 SARS-CoV-2 viral samples were analyzed thoroughly. We mostly found B.1.617 and its sub-lineages in the genomic sequencing results. RESULTS AND INTERPRETATION: On further analysis of patient data, it was seen that nine patients had been vaccinated against the SARS-CoV-2 previously. These nine patients had B.1.617/B.1 or A strains, and all of them had similar genomic variations in spike proteins as well as non-structural proteins (NSPs). The mutations seen in these sequences in the Spike (S), NSPs, and open reading frame (ORF) regions would have produced amino acid changes known to improve viral replication, confer drug resistance, influence host-cell interaction, and lead to antigenic drift. CONCLUSIONS: Increased virulence culminating in vaccine immunity evasion may be inferred from these specific mutations. Our study adds to the growing body of evidence linking rapidly emerging mutations in the S (Spike) and ORF genes of the SARS-CoV-2 genome to immune evasion.

Prognostic Role of Procalcitonin and C-reactive Protein in Surgical Neonates: A Single-Institution Experience.

Introduction Neonatal sepsis is a dynamic process where the rigorous evaluation of clinical signs along with appropriately selected biomarkers guides the diagnosis of sepsis. Procalcitonin (PCT) and C-reactive protein (CRP) are the two most commonly used diagnostic biomarkers used in sepsis. Sepsis remains the most important cause of mortality and morbidity in surgical neonates. A cross-sectional study was conducted to assess the prognostic predictability of PCT and CRP in neonatal surgical sepsis. Methods All the neonates admitted to the neonatal surgical intensive care unit between January 2019 and December 2020 with features of sepsis were included in the study. Blood cultures, CRP, and PCT on Day one (PCT1) and Day three (PCT3) of suspicion of sepsis were evaluated. The receiver operating characteristics curve was studied to estimate the probability of two markers to predict the mortality in neonatal sepsis. Results Of 102 surgical neonates, 63 neonates had early-onset sepsis while 23 (22.5%) neonates died and 30 neonates reported positive blood culture. There was a decline in the overall PCT trend from PCT1 and PCT3, while a significant PCT rise was noted for the non-survival group (p= 0.003). At cut-off of 5 mg/dl for CRP and 2.5 ng/dl for PCT1 and PCT3, the sensitivity (36.0%, 25.8%, 100%), specificity (84.1%, 83.3%, 97.5%), positive predictive value (52.2%, 73.9%, 91.3%), and negative predictive values (73.4%, 38.0%, 100%) were observed. Conclusion PCT on Day three of suspected sepsis has higher sensitivity, specificity, and accuracy for prognostication of surgical neonatal sepsis at the cut-off value of 2.5 ng/ml. The rising trend of PCT levels is indicative of a poor prognosis.

Elevated Circulatory Proline to Glutamine Ratio (PQR) in Endometriosis and Its Potential as a Diagnostic Biomarker.

Endometriosis (EM) is a hormone-dependent gynecological disease associated with chronic pelvic pain and altered immuno-inflammatory processes. It shares some cancer-like characteristics such as increased proline biosynthesis and activated glutaminolysis. Both proline and glutamine are interconvertible metabolically, and studies have shown their roles in cancer cell metabolic reprogramming, redox homeostasis, occurrence/development of endometrial carcinoma, and its further progression toward the malignant state. So based on this, we hypothesized that the circulatory proline to glutamine ratio (PQR) would be altered in EM and may serve as an indicative biomarker to improve the clinical diagnosis of EM. In present study, the circulatory-PQR levels were estimated for 39 EM patients and 48 age matched healthy female subjects using 800 MHz NMR spectroscopy. Among 39 EM patients, 15 were in the clinical stages I to II and referred to here as moderate EM (MEM) patients and 24 were in the clinical stages III to IV and referred here as severe EM (SEM) patients. The circulatory-PQR levels were significantly increased in EM patients (0.99 ± 0.13 µM in MEM; 1.39 ± 0.22 µM in SEM) compared to normal control (NC) subjects (0.52 ± 0.05 µM in NC). Further, the circulatory PQR levels exhibit the highest diagnostic potential with area under receiver operating characteristic (AUROC) curve values equal to 0.87 ± 0.04 [95%CI = 0.79-0.96] for MEM and 0.89 ± 0.04 [95% CI = 0.82-0.96] for SEM. These results suggested that circulatory-PQR has significant potential to serve as a noninvasive biomarker for diagnostic/prognostic screening of EM and further underscored the importance of these two nonessential amino acids (proline and glutamine) in cancer metabolism.

To Determine the Genotyping of Fc-gamma Receptor FCGR2A Polymorphism as Genetic Susceptibility to Neonatal Sepsis: A Study from a Tertiary Center of North India.

Background: Neonatal sepsis term is an infection of newborns <28 days of age. It is a common cause of death in developing countries. The receptor-gamma receptor FCGR2A has been shown to be associated with neonatal sepsis. It is an activating receptor found in many cell types such as monocytes, neutrophils, macrophages, platelets, and others. The receptor has a polymorphism (single-nucleotide polymorphism rs1801274) in its gene (FCGR2A) that encodes either a histidine (H) or arginine (R) at amino acid position 131. There are many studies showing the impact of these FCGR2A polymorphisms on sepsis. Our study aims to determine the prevalence of Fc-gamma receptor FCGR2A (rs1801274) polymorphism in neonatal sepsis and control in Eastern UP populations. Patients and Methods: We conducted a cross-sectional descriptive study of 590 patients (310 healthy individuals and 280 sepsis patients) to determine polymorphisms in the CD32A coding region in neonates. All individuals were genotyped for a variant at position 131 of the FcγRIIA gene. Discussion: In our study, the prevalence of FcγRIIa polymorphism is more in neonates with sepsis than in noninfected neonates. It was observed that the heterozygous allele (AG) were significantly increased in septic neonates when compared to the normal. Conclusion: Our data indicate that FcγRIIA genotyping can be used as a marker of genetic susceptibility to sepsis.

Genomic analysis of SARS-CoV-2 breakthrough infections from Varanasi, India

Studies worldwide have shown that the available vaccines are highly effective against SARS-CoV-2. However, there are growing laboratory reports that the newer variants of concerns (VOCs e.g. Alpha, Beta, Delta etc) may evade vaccine induced defense. In addition to that, there are few ground reports on health workers having breakthrough infections. In order to understand VOC driven breakthrough infection we investigated 14 individuals who tested positive for SARS-CoV-2 after being administered a single or double dose of Covishield (ChAdOx1, Serum Institute of India) from the city of Varanasi, which is located in the Indian state of Uttar Pradesh. Genomic analysis revealed that 78.6% (11/14) of the patients were infected with the B.1.617.2 (Delta) variant. Notably, the frequency (37%) of this variant in the region was significantly lower (p<0.01), suggesting that the vaccinated people were asymmetrically infected with the Delta variant. Most of the patients tested displayed mild symptoms, indicating that even a single dose of the vaccine can help in reducing the severity of the disease. However, more comprehensive epidemiological studies are required to understand the effectiveness of vaccines against the newer VOCs.