Showing papers in "Journal of Medical Virology in 2022"

Omicron variant of SARS‐CoV‐2: Genomics, transmissibility, and responses to current COVID‐19 vaccines

Abstract: Currently, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has spread worldwide as an Omicron variant. This variant is a heavily mutated virus and designated as a variant of concern by the World Health Organization (WHO). WHO cautioned that the Omicron variant of SARS‐CoV‐2 held a very high risk of infection, reigniting anxieties about the economy's recovery from the 2‐year pandemic. The extensively mutated Omicron variant is likely to spread internationally, posing a high risk of infection surges with serious repercussions in some areas. According to preliminary data, the Omicron variant of SARS‐CoV‐2 has a higher risk of reinfection. On the other hand, whether the current COVID‐19 vaccines could effectively resist the new strain is still under investigation. However, there is very limited information on the current situation of the Omicron variant, such as genomics, transmissibility, efficacy of vaccines, treatment, and management. This review focused on the genomics, transmission, and effectiveness of vaccines against the Omicron variant, which will be helpful for further investigation of a new variant of SARS‐CoV‐2.

The emergence and epidemic characteristics of the highly mutated SARS‐CoV‐2 Omicron variant

Abstract: Recently, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron variant (B.1.1.529) was first identified in Botswana in November 2021. It was first reported to the World Health Organization (WHO) on November 24. On November 26, 2021, according to the advice of scientists who are part of the WHO's Technical Advisory Group on SARS‐CoV‐2 Virus Evolution (TAG‐VE), the WHO defined the strain as a variant of concern (VOC) and named it Omicron. Compared to the other four VOCs (Alpha, Beta, Gamma, and Delta), the Omicron variant was the most highly mutated strain, with 50 mutations accumulated throughout the genome. The Omicron variant contains at least 32 mutations in the spike protein, which was twice as many as the Delta variant. Studies have shown that carrying many mutations can increase infectivity and immune escape of the Omicron variant compared with the early wild‐type strain and the other four VOCs. The Omicron variant is becoming the dominant strain in many countries worldwide and brings new challenges to preventing and controlling coronavirus disease 2019 (COVID‐19). The current review article aims to analyze and summarize information data about the biological characteristics of amino acid mutations, the epidemic characteristics, immune escape, and vaccine reactivity of the Omicron variant, hoping to provide a scientific reference for monitoring, prevention, and vaccine development strategies for the Omicron variant.

Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-A systematic review and meta-analysis.

Abstract: There is an established literature on the symptoms and complications of COVID-19 but the after-effects of COVID-19 are not well understood with few studies reporting persistent symptoms and quality of life. We aim to evaluate the pooled prevalence of poor quality of life in post-acute COVID-19 syndrome (PCS) and conducted meta-regression to evaluate the effects of persistent symptoms and intensive care unit (ICU) admission on the poor quality of life. We extracted data from observational studies describing persistent symptoms and quality of life in post-COVID-19 patients from March 10, 2020, to March 10, 2021, following PRISMA guidelines with a consensus of two independent reviewers. We calculated the pooled prevalence with 95% confidence interval (CI) and created forest plots using random-effects models. A total of 12 studies with 4828 PCS patients were included. We found that amongst PCS patients, the pooled prevalence of poor quality of life (EQ-VAS) was (59%; 95% CI: 42%-75%). Based on individual factors in the EQ-5D-5L questionnaire, the prevalence of mobility was (36, 10-67), personal care (8, 1-21), usual quality (28, 2-65), pain/discomfort (42, 28-55), and anxiety/depression (38, 19-58). The prevalence of persistent symptoms was fatigue (64, 54-73), dyspnea (39.5, 20-60), anosmia (20, 15-24), arthralgia (24.3, 14-36), headache (21, 3-47), sleep disturbances (47, 7-89), and mental health (14.5, 4-29). Meta-regression analysis showed the poor quality of life was significantly higher among post-COVID-19 patients with ICU admission (p = 0.004) and fatigue (p = 0.0015). Our study concludes that PCS is associated with poor quality of life, persistent symptoms including fatigue, dyspnea, anosmia, sleep disturbances, and worse mental health. This suggests that we need more research on PCS patients to understand the risk factors causing it and eventually leading to poor quality of life.

Epidemiological trends and clinical features of the ongoing monkeypox epidemic: A preliminary pooled data analysis and literature review

Abstract: An emerging outbreak of monkeypox infection is quickly spreading worldwide, being currently reported in more than 30 countries, with slightly less than 1000 cases. In the present preliminary report, we collected and synthesized early data concerning epidemiological trends and clinical features of the ongoing outbreak and we compared them with those of previous outbreaks. Data were pooled from six clusters in Italy, Australia, the Czech Republic, Portugal, and the United Kingdom, totaling 124 cases (for 35 of which it was possible to retrieve detailed information). The ongoing epidemic differs from previous outbreaks in terms of age (54.29% of individuals in their thirties), sex/gender (most cases being males), risk factors, and transmission route, with sexual transmission being highly likely. Also, the clinical presentation is atypical and unusual, being characterized by anogenital lesions and rashes that relatively spare the face and extremities. The most prevalent sign/symptom reported was fever (in 54.29% of cases) followed by inguinal lymphadenopathy (45.71%) and exanthema (40.00%). Asthenia, fatigue, and headache were described in 22.86% and 25.71% of the subjects, respectively. Myalgia was present in 17.14% of the cases. Both genital and anal lesions (ulcers and vesicles) were reported in 31.43% of the cases. Finally, cervical lymphadenopathy was described in 11.43% of the sample, while the least commonly reported symptoms were diarrhea and axillary lymphadenopathy (5.71% of the case series for both symptoms). Some preliminary risk factors can be identified (being a young male, having sex with other men, engaging in risky behaviors and activities, including condomless sex, human immunodeficiency virus positivity (54.29% of the sample analyzed), and a story of previous sexually transmitted infections, including syphilis). On the other hand, being fully virally suppressed and undetectable may protect against a more severe infectious course. However, further research in the field is urgently needed.

Characterization of the novel SARS‐CoV‐2 Omicron (B.1.1.529) variant of concern and its global perspective

Abstract: As the latest identified novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC), the influence of Omicron on our globe grows promptly. Compared with the last VOC (Delta variant), more mutations were identified, which may address the characteristics of Omicron. Considering these crucial mutations and their implications including an increase in transmissibility, COVID-19 severity, and reduction of efficacy of currently available diagnostics, vaccines, and therapeutics, Omicron has been classified as one of the VOC. Notably, 15 of these mutations reside in the receptor-binding domain of spike glycoprotein, which may alter transmissibility, infectivity, neutralizing antibody escape, and vaccine breakthrough cases of COVID-19. Therefore, our present study characterizes the mutational hotspots of the Omicron variant in comparison with the Delta variant of SARS-CoV-2. Furthermore, detailed information was analyzed to characterize the global perspective of Omicron, including transmission dynamic, effect on testing, and immunity, which shall promote the progress of the clinical application and basic research. Collectively, our data suggest that due to continuous variation in the spike glycoprotein sequences, the use of coronavirus-specific attachment inhibitors may not be the current choice of therapy for emerging SARS-CoV-2 VOCs. Hence, we need to proceed with a sense of urgency in this matter.

Relative instantaneous reproduction number of Omicron SARS‐CoV‐2 variant with respect to the Delta variant in Denmark

Abstract: The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become widespread across the world in a flashing manner. As of December 7, 2021, a total of 758 Omicron cases were confirmed in Denmark. Using the nucleotide sequences of the Delta and Omicron variants registered from Denmark in the GISAID database, we found that the effective (instantaneous) reproduction number of Omicron is 3.19 (95% confidence interval [CI]: 2.82–3.61) times greater than that of Delta under the same epidemiological conditions. The proportion of Omicron infections among all SARS-CoV-2 infections in Denmark was expected to exceed 95% on December 28, 2021, with a 95% CI from December 25 to December 31, 2021. Given that the Delta variant or variants less transmissible than Delta are dominant in most countries, the rapid increase in Omicron in the virus population may be observed as soon as the Omicron is introduced. Preparing proactive control measures is vital, assuming the substantial advantage of the transmission by Omicron.

Current evidence on efficacy of COVID‐19 booster dose vaccination against the Omicron variant: A systematic review

Abstract: Coronavirus disease 2019 (COVID‐19) is an ongoing pandemic, which affected around 45 million confirmed cases of COVID‐19, including more than 6 million deaths. However, on November 24, 2021, the World Health Organization announced a new severe acute respiratory syndrome coronavirus 2 variant designated as the B.1.1.529, a variant of concern (VOC), and the variant has been named as “Omicron.” Available preliminary evidence suggests that, as compared with previous VOCs, it has an increased risk of infectivity. Studies have shown that protection from various vaccines effectiveness against hospitalization and death from severe COVID‐19 disease is decreasing slowly after a two‐dose schedule of COVID‐19 vaccines. In response to experiencing a new COVID‐19 variant and ongoing resurgence of cases, the importance of COVID‐19 vaccine booster dose and durability of the effect of the third dose of vaccine against COVID‐19 Omicron variant is controversial yet. To address this, we conducted a systematic literature survey on effectiveness of the third or booster dose of COVID‐19 vaccine against the Omicron variant. We have performed a systematic search in PubMed (Medline), Google Scholar, and MedRXiv database, from inception to January 2022 using the MeSH terms and keywords “Corona Virus Disease‐2019 OR COVID‐19 AND Omicron AND COVID‐19 Booster Vaccine.” We have identified a total of 27 published studies. We have reviewed all the eligible available studies on the effectiveness of the COVID‐19 vaccine booster shots against the Omicron variant. This review may be helpful in accelerating the COVID‐19 booster dose vaccination.

Emergence of Omicron third lineage BA.3 and its importance

Abstract: In November 2021, Omicron, discovered in Botswana1 and classified as the fifth variant of concern (VOC)2, 3 by the World Health Organization (WHO) on November 26, 2021, the most mutated variant of SARS-CoV-2, has now circulated in 150 countries/territories until January 8, 2022, with 552,191 confirmed cases and causing 115 deaths4. Omicron was recently divided into three lineages (BA.1, BA.2, and BA.3)5. The differences between the BA.1 and BA.2 lineages are explored 6. Here we describe how these three lineages differ in their spike protein. Our study found that there were no specific mutations for the BA.3 lineage in spike protein. Instead, it is a combination of mutations in BA.1 and BA.2 spike proteins. This article is protected by copyright. All rights reserved.

Omicron (BA.1) and sub‐variants (BA.1.1, BA.2, and BA.3) of SARS‐CoV‐2 spike infectivity and pathogenicity: A comparative sequence and structural‐based computational assessment

Abstract: The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread throughout the world. We used computational tools to assess the spike infectivity, transmission, and pathogenicity of Omicron (BA.1) and sub-variants (BA.1.1, BA.2, and BA.3) in this study. BA.1 has 39 mutations, BA.1.1 has 40 mutations, BA.2 has 31 mutations, and BA.3 has 34 mutations, with 21 shared mutations between all. We observed 11 common mutations in Omicron’s receptor-binding domain and sub-variants. In pathogenicity analysis, the Y505H, N786K, T95I, N211I, N856K, and V213R mutations in omicron and sub-variants are predicted to be deleterious. Due to the major effect of the mutations characterising, in the receptor-binding domain (RBD), we found that Omicron and sub-variants had a higher positive electrostatic surface potential. This could increase interaction between RBD and electronegative human angiotensin-converting enzyme 2 (hACE2). Omicron and sub-variants had a higher affinity for hACE2 and the potential for increased transmission when compared to the wild type. Among Omicron sub-lineages, BA.2 and BA.3 have a higher transmission potential than BA.1 and BA.1.1. We predicted that mutated residues in BA.1.1 (K478), BA.2 (R400, R490, R495), and BA.3 (R397 and H499) formation of new salt bridges and hydrogen bonds. Omicron and sub-variant mutations at Receptor-binding Motif (RBM) residues such as Q493R, N501Y, Q498, T478K, and Y505H all contribute significantly to binding affinity with human ACE2. Interactions with Omicron variant mutations at residues 493, 496, 498, and 501 seem to restore ACE2 binding effectiveness lost due to other mutations like K417N and Y505H.

Re‐emerging human monkeypox: A major public‐health debacle

Abstract: A multicountry outbreak of the monkeypox virus has gained global attention. As of May 25, 250 confirmed human monkeypox cases have been reported globally. Monkeypox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. Monkeypox is often a self‐limiting infection, with symptoms lasting 2–4 weeks with the case fatality ratio around 3%–6%. Monkeypox is transmitted to humans by direct contact with an infected person or animal or contact with virus‐contaminated material. Human monkeypox infections may lead to various medical complications such as fever, rash, and lymphadenopathies. Pneumonitis, encephalitis, sight‐threatening keratitis, and subsequent bacterial infections are all possible complications of monkeypox. An antiviral agent developed to treat smallpox has also been approved for use in the treatment of monkeypox in the United States. Vaccines used in the smallpox eradication program also provided immunity to monkeypox. Newer vaccines have been developed, one of which has been approved for monkeypox prevention. In this study, we provide information about the recent outbreaks of human monkeypox, epidemiology, transmission pattern, possible diagnosis techniques, therapeutics, and available preventive strategies.

A large‐scale meta‐analytic atlas of mental health problems prevalence during the COVID‐19 early pandemic

Abstract: The COVID-19 pandemic and related restrictions can impact mental health. To quantify the mental health burden of COVID-19 pandemic, we conducted a systematic review and meta-analysis, searching World Health Organization COVID-19/PsycInfo/PubMed databases (09/29/2020), including observational studies reporting on mental health outcomes in any population affected by COVID-19. Primary outcomes were the prevalence of anxiety, depression, stress, sleep problems, posttraumatic symptoms. Sensitivity analyses were conducted on severe mental health problems, in high-quality studies, and in representative samples. Subgroup analyses were conducted stratified by age, sex, country income level, and COVID-19 infection status. One-hundred-seventy-three studies from February to July 2020 were included (n = 502,261, median sample = 948, age = 34.4 years, females = 63%). Ninety-one percent were cross-sectional studies, and 18.5%/57.2% were of high/moderate quality. The highest prevalence emerged for posttraumatic symptoms in COVID-19 infected people (94%), followed by behavioral problems in those with prior mental disorders (77%), fear in healthcare workers (71%), anxiety in caregivers/family members of people with COVID-19 (42%), general health/social contact/passive coping style in the general population (38%), depression in those with prior somatic disorders (37%), and fear in other-than-healthcare workers (29%). Females and people with COVID-19 infection had higher rates of almost all outcomes; college students/young adults of anxiety, depression, sleep problems, suicidal ideation; adults of fear and posttraumatic symptoms. Anxiety, depression, and posttraumatic symptoms were more prevalent in low-/middle-income countries, sleep problems in high-income countries. The COVID-19 pandemic adversely impacts mental health in a unique manner across population subgroups. Our results inform tailored preventive strategies and interventions to mitigate current, future, and transgenerational adverse mental health of the COVID-19 pandemic.

Correlation between a quantitative anti-SARS-CoV-2 IgG ELISA and neutralization activity.

Abstract: In the current COVID-19 pandemic, a better understanding of the relationship between merely binding and functionally neutralizing antibodies is necessary to characterize protective antiviral immunity following infection or vaccination. This study analyzes the level of correlation between the novel quantitative EUROIMMUN Anti-SARS-CoV-2 QuantiVac ELISA (IgG) and a microneutralization assay. A panel of 123 plasma samples from a COVID-19 outbreak study population, preselected by semiquantitative anti-SARS-CoV-2 IgG testing, was used to assess the relationship between the novel quantitative ELISA (IgG) and a microneutralization assay. Binding IgG targeting the S1 antigen was detected in 106 (86.2%) samples using the QuantiVac ELISA, while 89 (72.4%) samples showed neutralizing antibody activity. Spearman's correlation analysis demonstrated a strong positive relationship between anti-S1 IgG levels and neutralizing antibody titers (rs = 0.819, p < 0.0001). High and low anti-S1 IgG levels were associated with a positive predictive value of 72.0% for high-titer neutralizing antibodies and a negative predictive value of 90.8% for low-titer neutralizing antibodies, respectively. These results substantiate the implementation of the QuantiVac ELISA to assess protective immunity following infection or vaccination.

The puzzling mutational landscape of the SARS‐2‐variant Omicron

Abstract: The recently emerging SARS‐CoV‐2 variant omicron displays an unusual association of 30 mutations, 3 deletions, and 1 insertion. To analyze the impact of this atypic mutational landscape, we constructed a complete structure of the omicron spike protein. Compared with the delta variant, the receptor‐binding domain (RBD) of omicron has an increased electrostatic surface potential, but a decreased affinity for the ACE‐2 receptor. The N‐terminal domain (NTD) has both a decreased surface potential and a lower affinity for lipid rafts. The omicron variant is predicted to be less fusogenic and thus less pathogenic than delta, due to a geometric reorganization of the S1‐S2 cleavage site. Overall, these virological parameters suggest that omicron does not have a significant infectivity advantage over the delta variant. However, in omicron, neutralizing epitopes are greatly affected, suggesting that current vaccines will probably confer little protection against this variant. In conclusion, the puzzling mutational pattern of the omicron variant combines contradictory properties which may either decrease (virological properties) or increase (immunological escape/facilitation) the transmission of this variant in the human population. This Janus‐like phenotype may explain some conflicting reports on the initial assessment of omicron and provide new insights about the molecular mechanisms controlling its dissemination and pathogenesis worldwide.

Genomic annotation and molecular evolution of monkeypox virus outbreak in 2022

Abstract: Monkeypox virus (MPXV) has generally circulated in West and Central Africa since its emergence. Recently, sporadic MPXV infections in several nonendemic countries have attracted widespread attention. Here, we conducted a systematic analysis of the recent outbreak of MPXV‐2022, including its genomic annotation and molecular evolution. The phylogenetic analysis indicated that the MPXV‐2022 strains belong to the same lineage of the MPXV strain isolated in 2018. However, compared with the MPXV strain in 2018, in total 46 new consensus mutations were observed in the MPXV‐2022 strains, including 24 nonsynonymous mutations. By assigning mutations to 187 proteins encoded by the MPXV genome, we found that 10 proteins in the MPXV are more prone to mutation, including D2L‐like, OPG023, OPG047, OPG071, OPG105, OPG109, A27L‐like, OPG153, OPG188, and OPG210 proteins. In the MPXV‐2022 strains, four and three nucleotide substitutions are observed in OPG105 and OPG210, respectively. Overall, our studies illustrated the genome evolution of the ongoing MPXV outbreak and pointed out novel mutations as a reference for further studies.

Omicron (B.1.1.529) variant of SARS‐CoV‐2: Concerns, challenges, and recent updates

Abstract: Highlights Omicron has shown immune escape from neutralizing antibodies generated through previous infection or vaccination. It could evade the protection provided by mAbs being used in clinics for treating coronavirus disease 2019 (COVID‐19) patients. Booster dose is recommended to elevate the protective levels of antibodies in COVID‐19 vaccinated individuals. The development of powerful oral antiviral drugs such as Molnupiravir and Paxlovid have shown promising clinical results and raised new hopes of COVID‐19 treatment. High efforts are being made to develop highly efficacious vaccines, and by implementing appropriate prevention and control strategies to counter Omicron.

Autoimmune complications of COVID-19.

Abstract: Coronavirus disease 2019 (COVID-19) is still propagating a year after the start of the pandemic. Besides the complications patients face during the COVID-19 disease period, there is an accumulating body of evidence concerning the late-onset complications of COVID-19, of which autoimmune manifestations have attracted remarkable attention from the first months of the pandemic. Autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, and the detection of autoantibodies are the cues to the discovery of the potential of COVID-19 in inducing autoimmunity. Clarification of the pathophysiology of COVID-19 injuries to the host, whether it is direct viral injury or autoimmunity, could help to develop appropriate treatment.

Mutational and phylogenetic analyses of the two lineages of the Omicron variant

Abstract: Based on the recommendation of the WHO's Technical Advisory Group on Virus Evolution, WHO designated the variant B.1.1.529 as a variant of concern (VOC) and named Omicron on 26 November, 2021. Omicron was first observed in Africa in mid-November 2021.1 The infection by this variant has been rapidly spreading and 85 countries have already reported the cases of human infection with this variant as of 15 December 2021.2 The rapid spread of Omicron has again fueled the fears of COVID-19 all around the world like other four VOCs (Alpha, Beta, Gamma, and Delta). Recently, the Omicron variant has classified into two different lineages BA.1 and BA.2 based on the mutations, some of which are common and some are unique to both lineages.3, 4 Still, there is no clear evidence or published article on the mutational diversity and phylogenetic analysis of these two lineages. Therefore, in the present study, we have performed the whole-genome mutational mapping and phylogenetic analysis of BA.1 and BA.2 lineages. We have downloaded 6 genome sequences each of BA.1 and BA.2, and also the genome sequence of the prototype strain (hCoV-19/Wuhan/WIV04/2019) from the Global Initiative on Sharing All Influenza Data (GISAID) and performed whole-genome mutational analysis according to the protocol described in Sarkar et al.5, 6 Each of the six genomes of both BA.1 and BA.2 lineages was found to have 51 mutations dispersed throughout the genome, 32 of which are common to both lineages, whereas each lineage has 19 signature mutations. Among 32 common mutations, 21 are present in the S glycoprotein and the rest 11 are present in the other four coding regions (ORF1ab, E, M, and N). Nineteen unique mutations of BA.1 include 13 in the S glycoprotein and that of BA.2 includes 7 in the S glycoprotein (Table 1). Phylogenetic analysis of 12 genome sequences of Omicron variant, encompassing 6 genomes each of BA.1 and BA.2, along with the 2000 genomes of 25 different clades by Ultrafast Sample placement of Existing tRees,6, 7 revealed that genomes of Omicron variant formed a new cluster that emerged from the 20B clade (also known as GR) and also subdivided into two different subclusters (BA.1 and BA.2) based on the unique mutations (Figure 1). The S glycoprotein mediates virus attachment to ACE2 receptor, membrane fusion, and entry into the host cell, and also acts as a primary target for neutralizing antibodies elicited by the host immune response.8 Presence of 34 and 28 mutations in the S glycoprotein of BA.1 and BA.2, respectively, raising concern whether these lineages have increased transmissibility, immune escape potential, and virulence compared to other circulating SARS-CoV-2 strains especially Delta which is currently dominating worldwide. Seven mutations of both BA.1 and BA.2 (G142D, K417N, T478K, N501Y, D614G, H655Y, and P681H) and three mutations of BA.1 (∆HV69del, T95I, and ∆YY144del) overlap four other VOCs (Alpha, Beta, Gamma, and Delta) and have previously been linked with high transmissibility, increased viral binding affinity, and immune evasion.9-12 Functional implication of the remaining mutations of the S glycoprotein and other coding regions of BA.1 and BA.2 still unknown, leaving a question of how the whole set of mutations of the two lineages will affect viral fitness. Preliminary evidence indicated that Omicron has increased infectivity and a high transmission rate compared to Delta.13-15 However, whether the rapid spread of Omicron in countries with increased population immunity is due to increased transmissibility and/or immune evasion remains unclear. Though, some recent studies have claimed the immune evasion properties of the Omicron.14-17 Based on this existing evidence, Omicron is anticipated to overtake Delta in areas where community transmission occurs. The severity of Omicron infection still remains elusive. Preliminary studies from South Africa suggested that Omicron may be less severe than Delta,18 and all COVID-19 patients, infected with Omicron, from countries of EU and EEA either showed mild symptoms or were asymptomatic.19 Detection accuracy of routinely used PCR and antigen-based rapid diagnostic test (Ag-RDT) assays was not found to be influenced by most of the Omicron strains. However, the BA.1 lineage showed S gene target failure (SGTF) in RT-PCR assay due to multiple deletions in the NTD of S glycoprotein, whereas BA.2 lineage may skip SGTF due to lack of deletions in the NTD. Overall, the global threat related to Omicron remains very high for its potential to escape humoral immune response and high transmissibility, which may lead to another wave of COVID-19 with severe consequences.19 The authors acknowledge the University Grants Commission (UGC) of India for providing fellowship to Swagata Majumdar. The authors would also like to acknowledge GISAID (https://www.gisaid.org/) for facilitating open data sharing. The authors declare that there are no conflict of interests. Swagata Majumdar and Rakesh Sarkar conceived the study. Swagata Majumdar performed sequence retrieval of SARS-CoV-2 and whole-genome mutational analysis. Rakesh Sarkar performed the phylogenetic analysis and drafted the manuscript. All authors revised the manuscript and approved the final manuscript for submission. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Characterization of the significant decline in humoral immune response six months post‐SARS‐CoV‐2 mRNA vaccination: A systematic review

Abstract: Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) messenger RNA (mRNA) vaccines such as Pfizer-BioNTech (mRNA BNT161b2) and Moderna (mRNA-1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti-SARS-CoV-2 antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of the literature was performed and a total of 18 articles (N = 15 980 participants) were identified and reviewed. The percent difference of means of reported antibody titers was then calculated to determine the decline in humoral response after the peak levels postvaccination. Findings revealed that the peak humoral response was reached at 21–28 days after the second dose, after which serum levels progressively diminished at 4–6-month postvaccination. Additionally, results showed that regardless of age, sex, serostatus, and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti-receptor binding domain immunoglobulin G (IgG) and anti-spike IgG, ranging from 94% to 95% at 90–180 days and 55%–85% at 140–160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient-related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns.

SARS‐CoV‐2 variants and vulnerability at the global level

Abstract: Numerous variants of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic have evolved. Viral variants may evolve with harmful susceptibility to the immunity established with the existing COVID‐19 vaccination. These variants are more transmissible, induce relatively extreme illness, have evasive immunological features, decrease neutralization using antibodies from vaccinated persons, and are more susceptible to re‐infection. The Centers for Disease Control and Prevention (CDC) has categorized SARS‐CoV‐2 mutations as variants of interest (VOI), variants of concern (VOC), and variants of high consequence (VOHC). At the moment, four VOC and many variants of interest have been defined and require constant observation. This review article summarizes various variants of SARS‐CoV‐2 surfaced with special emphasis on VOCs that are spreading across the world, as well as several viral mutational impacts and how these modifications alter the properties of the virus.

Culture and identification of a “Deltamicron” SARS‐CoV‐2 in a three cases cluster in southern France

Abstract: Multiple SARS‐CoV‐2 variants have successively, or concomitantly spread worldwide since the summer of 2020. A few co‐infections with different variants were reported and genetic recombinations, common among coronaviruses, were reported or suspected based on co‐detection of signature mutations of different variants in a given genome. Here we report three infections in southern France with a Delta 21J_AY.4‐Omicron 21K/BA.1 “Deltamicron” recombinant. The hybrid genome harbors signature mutations of the two lineages, supported by a mean sequencing depth of 1163–1421 reads and a mean nucleotide diversity of 0.1%–0.6%. It is composed of the near full‐length spike gene (from codons 156–179) of an Omicron 21K/BA.1 variant in a Delta 21J/AY.4 lineage backbone. Importantly, we cultured an isolate of this recombinant and sequenced its genome. It was observed by scanning electron microscopy. As it is misidentified with current variant screening quantitative polymerase chain reaction (qPCR), we designed and implemented for routine diagnosis a specific duplex qPCR. Finally, structural analysis of the recombinant spike suggested its hybrid content could optimize viral binding to the host cell membrane. These findings prompt further studies of the virological, epidemiological, and clinical features of this recombinant.

Twin combination of Omicron and Delta variants triggering a tsunami wave of ever high surges in COVID‐19 cases: A challenging global threat with a special focus on the Indian subcontinent

Abstract: The emergence of Omicron (B.1.1.529) variant of SARS‐CoV‐2 has resulted into a very massive surge in COVID‐19 cases worldwide. Due to continuous emergence of multiple variants of SARS‐CoV‐2, the ongoing pandemic has caused severe morbidity and mortality in last two years. The rate of infectivity of Omicron variant is much higher than Delta variant and in a very quick time Omicron has displaced the Delta variant and now become a dominant variant across the globe. The twin combination of Omicron and Delta variant is triggering a Tsunami wave of ever high surges in COVID‐19 cases worldwide. This article highlights the global threats and challenges posed by Omicron, and strategies to counter it with a particular focus on Indian sub‐continent.

A third booster dose may be necessary to mitigate neutralizing antibody fading after inoculation with two doses of an inactivated SARS-CoV-2 vaccine.

Abstract: Neutralizing antibodies in volunteers who received two doses of an inactivated SARS-CoV-2 vaccine deceased over several months. A three-dose procedure study suggested that the boost conferred by a third dose rescued the waning of neutralizing antibodies after the two doses of the inactivated vaccine. Importantly, a booster dose can also elicit a more robust neutralizing antibody response than the two-dose procedure. This article is protected by copyright. All rights reserved.

Characteristics of the first 1119 SARS‐CoV‐2 Omicron variant cases, in Marseille, France, November−December 2021

Abstract: One thousand one hundred and nineteen cases of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron variant cases have been diagnosed at the Institut Hospitalo‐Universitaire Méditerranée Infection, Marseille, France, between November 28, 2021, and December 31, 2021. Among the 825 patients with known vaccination status, 383 (46.4%) were vaccinated, of whom 91.9% had received at least two doses of the vaccine. Interestingly, 26.3% of cases developed SARS‐CoV‐2 infection within 21 days following the last dose of vaccine suggesting possible early production of anti‐SARS‐CoV‐2 facilitating antibodies. Twenty‐one patients have been hospitalized, one patient required intensive care, and another patient who received a vaccine booster dose died.

Monkeypox: A potential global threat?

Abstract: Monkeypox, a largely neglected disease endemic in Western and Central Africa, has recently attracted global attention due to over 100 confirmed and suspected cases (by May 21, 2022) in more than ten countries in Europe, North America, and Australia. This article is protected by copyright. All rights reserved.

Omicron (B.1.1.529 variant of SARS‐CoV‐2); an emerging threat: Current global scenario

Abstract: The Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its various emerging variants, is posing very high health threats with its continued pandemic waves with 5.5 millions deaths out of 272 million confirmed cases reported worldwide as of December 17, 2021, and recently again a rapid surge of cases is being seen at global level.1-4 After the Alpha, Beta, Gamma, and Delta SARS-CoV-2 variant of concerns (VOCs), the most recent B.1.1.529 variant (named as Omicron) is classified as VOC by WHO on November 26, 2021, is creating alarming situations worldwide. The first case of Omicron was documented from Botswana, South Africa in early November month, and within a very short time this variant has now spread rapidly to 108 countries with nearly 1.5 lakh reported cases and 26 deaths as on December 25, 2021.5-9 Various studies are being carried out to investigate the theories and hypothesis underlying the emergence of the Omicron variant such as several mutations might have accumulated in chronically infected persons, lesser-studied human population, in animal reservoirs, diverse evolutionary mechanisms, intra-host adaptation, various immune pressures, insufficient vaccination rates, larger population of immunocompromised persons, and other predisposing factors that could provide an ideal situation for the emergence of newer variants.10-14 Omicron is the most mutated SARS-CoV-2 variant possessing 50 mutations in its genome including 30 mutations in its spike (S) protein alone, owing to which it gained higher transmissibility and partial resistance to immunity induced by currently available COVID-19 vaccines and antibody-based therapies.15-21 The omicron variant is detected by RT-PCR,22 however genomic sequencing is required for confirmation. Preliminary evidence also suggests an increased risk of reinfection in COVID-19 recovered patients as well as vaccine breakthrough in vaccinated individuals with this variant. Altogether, the high genetic changes will affect virus characteristics such as of acquiring higher transmissibility, disease severity, immune escape from vaccine and immunotherapies based protection and impeding diagnostics. Therefore, it is highly recommended to enhance the global surveillance and sequencing efforts to understand circulating SARS-CoV-2 variants with a particular focus on Omicron. Until now, Omicron has been reported to cause asymptomatic infection or a milder disease with earliest common symptoms such as sore throat, headache, running nose, body ache, fever, and fatigue/weakness.23 In South Africa, Omicron has 80% lower risk of hospitalization as per report. Cases of infections with Omicron are on rise but fewer hospital admissions are observed as compared to delta variant in South Africa.24 The increasing positive electric charge in the crucial regions of S protein of Omicron may facilitate viral infection of the host cell.25 Moreover, this emerging variant does not raise significantly the risk of severity and death in vaccinated people,26 however, it is too early to conclude. As the Alpha, Beta, and Delta variants were associated with consecutive waves of SARS-CoV-2 infections across the entire world with high surge of COVID-19 cases and associated deaths seen during first half of this year, so it is expected that the world may face a new wave of pandemic due to Omicron in the coming time owing to its very rapid spread in many countries.27 Now the COVID-19 cases are increasing rapidly in South Africa and the early doubling time is higher than that of the previous three waves of COVID-19 pandemic.8, 28, 29 As on December 24, the UK reported maximum Omicron cases (26,447) followed by the USA (4614), Denmark (2001), South Africa (1643), and Australia (859) while cases are also increasing on daily basis in other many countries.7 As per the Institute for Health Metrics and Evaluation (IHME, the USA), world will witness 300 crore Omicron cases globally in next 2 months however, the infection-fatality rate will be lower than the Delta variant.30 Now, Omicron has become the dominant variant and found in more than 70% of the samples collected in the United States, and it may likely displace Delta as the dominant variant in the coming days.31 So, the international responses towards Omicron have been raised as compared to other previous variants. Due to the seasonal influenza (already been reported), the coming winter will be more challenging and will bring triple respiratory virus threat (Omicron, Delta, and influenza).31 As on today (December 25, 2021) the USA and UK reported more than lakhs of COVID-19 cases daily. The COVID-19 vaccines are based on the SARS-CoV-2 spike receptor-binding domain (RBD). The Beta variant has three mutations and Delta variant has two mutations, however, Omicron has 10 to 15 mutations in this region. The COVID-19 vaccines were found less effective against Beta and Delta variants as the mutations facilitated the virus variants to partially evade immune responses.15 In case of this newer variant (Omicron), many such functions and impacts of higher mutations on efficacy of vaccines are yet to be analyzed. Researchers are trying to understand whether antibodies produced from vaccination can neutralize Omicron variant and upto what extent the currently available COVID-19 vaccines and immunotherapies will be efficacious,18, 19, 32 time will answer all these questions. Moreover, Zhang and coworkers have suggested that Omicron may lead to more significant escape from immune protection.20 In between this, the vaccine vendors have also announced their plans to make new versions of their COVID-19 vaccines tailored to Omicron.15 In this context, Moderna and Pfizer have declared to produce specific vaccines for omicron within 100 days.26 Booster doses are being recommended to increase the protective potentials of COVID-19 vaccines and preventing health impacts of infection with Omicron variant as well as other variants.33, 34 There is also a need to design and validate potent commercial immunoassays for detecting anti-SARS-CoV-2 spike and RBD antibodies against the newly emerging and highly mutated variants such as Omicron.35 A recent study also suggests that the Omicron variant of SARS-CoV-2 encodes 37 amino acid substitutions in the spike protein, out of which 15 are in RBD region and the Omicron RBD binds to human ACE2 with increased affinity.36 Still vaccine inequity and hesitancy are the influential factors for the emergence of such novel variants and their transmission. Omicron variant was first identified in India from the specimen collected from a 37-year-old man who came from South Africa on November 25. Thereafter, 415 cases of Omicron have been detected from different states (mainly from Maharashtra, Delhi, Gujarat, and Telangana) as on December 25, 2021. It is important to note that most of the reported Omicron infected individuals are already vaccinated. The rate of infectivity of Omicron variant is five times more than Delta variant.15 Moreover, Omicron may be twice more likely to escape currently available COVID-19 vaccines as compared to the Delta variant.37 So, vaccines are not only the sufficient way to control the transmission, we also need face mask, sanitizer, and surveillance to break the transmission.38 It is uncertain that whether it will cause more disease severity or not. India is the second most populated country and the people are still not obeying the appropriate COVID-19 guidelines. The vaccine booster program is not started and only 41.8% people are fully vaccinated (taken two doses) while 60.7% people have received the first dose in India as on December 25, 2021.39 The huge rapid surge of COVID-19 cases and deaths during second wave of pandemic in India owing to evolution and emergence of Delta variant of SARS-CoV-2, lesser vaccine coverage at time, mass gathering events happening in festivals and religious ceremonies, rushes in markets and crowding at other places while lowering down the COVID-19 appropriate behaviors of wearing masks and social distancing by the public during routine activities. The Delta variant is also responsible for surging multiple fresh waves throughout the world from time to time and hence the pandemic is still ongoing despite promoting massive vaccination drives at global level. Recently, schools and colleges have been reopened in offline mode as well as all other official and private organizations are functioning routinely. In this context, 53 girl students (of VIII, IX, X class) of St. Marys Girls High School were infected with SARS-CoV-2 recently.40 Moreover, 54 medical students of Veer Surendra Sai Institute of Medical Sciences and Research (VIMSAR) were detected COVID-19 positive after attending college annual function.41 Recently, 16 students (of VIII, IX, X, XI class) of Maha school at Ghansoli in Mumbai have also tested positive.42 As the classes are started in offline mode, so, COVID-19 cases are rising in several educational institutes.43 So, obeying COVID-19 guidelines to the desired levels by students in schools and colleges are really challenging in Indian school settings.44 Moreover, such students have not taken COVID-19 vaccines yet. Under these situations, the Omicron variant may infect younger populations. The government, authorities, and parents must be careful on this issue to protect students amid spread and rising cases of this newly emerged variant. This new variant (Omicron) has now started its game and may potentially circulate to larger population owing to its higher transmissibility and might be in future become responsible for another wave (the so-called third wave) of the COVID-19 pandemic. Amid such high threats of the micron variants, urgent and utmost priority need to be given for enhancing genomic surveillance, strictly implement the recommended prevention and control strategies including testing and isolation, wearing of face mask, hand hygiene, social distancing, speeding up vaccination programs and opting for booster doses for all, developing highly efficacious vaccines, attempting for designing multivariant (multiple antigen-based), and mutation-proof vaccines, and potent immunotherapies, so as to limit the dangers of Omicron and other variants well before facing the surge in COVID-19 cases as third wave in the country. As per initial data, cases of Omicron infected patients in India are mainly males as compared to females. Indian government has implemented strict measures for the travelers from South Africa and risk countries, and imposed necessary bans on international flights. Due to this new variant, some countries quickly closed their borders for foreign travelers, while other countries enforced quarantine for the travellers coming from South Africa and neighboring countries.29 After the death of an Omicron-infected patient confirmed by the UK Health Security Agency (UKHSA), the UK announced a third COVID-19 vaccine dose for their adults.26 The UK government has also announced wearing of face masks again as compulsory on public transport and in shops and schools. People contacted with an Omicron infected patient will be required to be isolated for 14 days. The government has expanded vaccine booster program to people under 40 years of age.45 The currently available COVID-19 vaccines may be less effective against the Omicron, however may provide some protection against Omicron. The general public has to take up full course of vaccination along with booster dose.45 It is highly recommended to develop more efficacious and protective vaccines at global level. The vaccination drive programs must be strictly implemented towards obtaining herd immunity. World Health Organization also reminded the individuals to take measures (physical distancing, hand hygiene, wearing well-fitting masks, avoiding crowded spaces, getting vaccinated, etc.) to reduce the risk of COVID-19 with such variants. Any failure to timely tackle the Omicron would facilitate continued emergence of newer SARS-CoV-2 variants which could give rise to as scenario of never-ending pandemic, therefore implementation of recommended COVID-19 prevention and control measures, wisely translating the gained knowledge of SARS-CoV-2 and designing newer and modified strategies are the need of the hour to counter Omicron with a holistic approach amid the ongoing pandemic.46-49 All the authors acknowledge and thank their respective institutes and universities of affiliation. The authors declare that there are no conflict of interests. Ranjan K. Mohapatra: Conceptualization, Writing- original draft. Ruchi Tiwari; Ashish K. Sarangi; Mohammad Azam: Data analysis and interpretation. Kuldeep Dhama; Venkataramana Kandi: Writing—review & editing. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Attaching a stigma to the LGBTQI+ community should be avoided during the monkeypox epidemic

Abstract: An outbreak of monkeypox, a rare zoonotic disease caused by an orthopoxvirus, is currently ongoing and has spread so far to more than 20 countries, mostly affecting Europe, the Americas, Australia, and Israel, with more than 400 confirmed cases ([https://bnonews.com/monkeypox/](https://bnonews.com/monkeypox/)), becoming the largest monkeypox epidemic outside of western and central Africa, where it is endemic in eleven countries [1]. In the UK, where the first monkeypox case was reported on May 7, 2022, in a traveler returning from Nigeria, the National "Health Security Agency" (UKHSA) has reported that "a notable proportion of early cases detected have been in gay and bisexual men and so UKHSA is urging this community in particular to be alert" ([https://www.gov.uk/government/news/monkeypox-cases-confirmed-in-england-latest-updates](https://www.gov.uk/government/news/monkeypox-cases-confirmed-in-england-latest-updates)). Maspalomas (Gran Canaria) 2022", held from May 5 to May 15, 2002, in Maspalomas, Great Canary (Spain), where about 80,000 people met from across the European continent. These mass gatherings were linked to the spread of the virus, while epidemiological investigations to determine the determinants of the transmission were still ongoing. Whereas in Africa, monkeypox cases are generally transmitted from infected animals, and human-to-human transmission began to emerge after the 1996-1997 outbreak in the Democratic Republic of Congo (DRC), linked to the discontinuation of vaccination against smallpox and the waning of immunity, poor hygiene and crowded living quarters, in developed countries other potential routes have been postulated, such as respiratory droplets, direct contact with mucocutaneous lesions, or fomites. This article is protected by copyright. All rights reserved.

Emerging evidence on Omicron (B.1.1.529) SARS‐CoV‐2 variant

Abstract: COVID's Omicron variant has sparked a slew of concerns across the globe. This review aims to provide a brief overview of what we know about the Omicron variant right now. The new variant has been discovered in 149 countries across all six World Health Organization (WHO) regions since its discovery in South Africa on November 24, 2021 and became the dominant variant in the country in less than 3 weeks. The WHO has warned that the B.1.1.529 variant is spreading at an unprecedented rate, and has urged countries to prepare for the worst. Over the course of this time, researchers from Africa and around the world have uncovered a wealth of information about the virus's epidemiology and biological properties. Case numbers are increasing exponentially in hard‐hit areas such as South Africa, United Kingdom, and USA (overtaking the delta variant), implying that the variant is highly transmissible. Initial research has provided some insights into the efficacy of vaccines against the Omicron variant and whether it produces major illness, however, much remains unknown, and additional work is needed to investigate what the initial reports represent in real‐world situations.

Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial.

Abstract: This trial aims to evaluate the effectiveness of adding melatonin to the treatment protocol of hospitalized coronavirus disease 2019 (COVID-19) patients. This was an open-label, randomized controlled clinical trial in hospitalized COVID-19 patients. Patients were randomized into a treatment arm receiving melatonin plus standard care or a control arm receiving standard care alone. The trial's primary endpoint was sleep quality examined by the Leeds Sleep Evaluation Questionnaire (LSEQ). The trial's secondary endpoints were symptoms alleviation by Day 7, intensive care unit admission, 10-day mortality, white blood cell count, lymphocyte count, C-reactive protein status, and peripheral capillary oxygen saturation. Ninety-six patients were recruited and allocated to either the melatonin arm (n = 48) or control arm (n = 48). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms on Day 7. The mean of the LSEQ scores was significantly higher in the melatonin group (p < 0.001). There was no significant difference in laboratory data, except for blood oxygen saturation, which has improved significantly in the melatonin group compared with the control group (95.81% vs. 93.65% respectively, p = 0.003). This clinical trial study showed that the combination of oral melatonin tablets and standard treatment could substantially improve sleep quality and blood oxygen saturation in hospitalized COVID-19 patients.

The global case fatality rate of coronavirus disease 2019 by continents and national income: A meta‐analysis

Abstract: The aim of this study is to provide a more accurate representation of COVID‐19's case fatality rate (CFR) by performing meta‐analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID‐19 for every country reporting COVID‐19 cases. On the basis of data, we performed random and fixed meta‐analyses for CFR of COVID‐19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed‐ and random‐model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random‐model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random‐model results showed an increase near 5.0%. In high‐income countries, pooled estimates and fixed‐model showed gradually increasing trends with a final pooled estimates and random‐model reached about 8.0% and 4.0%, respectively. In middle‐income, the pooled estimates and fixed‐model have gradually increased reaching up to 4.5%. in low‐income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID‐19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.