Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1–3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans. Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.

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A new coronavirus associated with human respiratory disease in China.

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4–28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7–13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic. Estimates of the levels of neutralizing antibodies necessary for protection against symptomatic SARS-CoV-2 or severe COVID-19 are a fraction of the mean level in convalescent serum and will be useful in guiding vaccine rollouts.

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Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.

Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets. The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been characterized by the emergence of mutations and so-called variants of concern that impact virus characteristics, including transmissibility and antigenicity. In this Review, members of the COVID-19 Genomics UK (COG-UK) Consortium and colleagues summarize mutations of the SARS-CoV-2 spike protein, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

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SARS-CoV-2 variants, spike mutations and immune escape.

Background The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to ...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2108891

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant.

The emergence of SARS-CoV-2 Delta variant and its derivatives has created grave public health problem worldwide. The high transmissibility associated with this variant has led to daily increase in the number of SARS-CoV-2 infections. Delta variant has slowly dominated the other variants of concern. Subsequently, Delta has further mutated to Delta AY.1 to Delta AY.126. Of these, Delta AY.1 has been reported from several countries including India and considered to be highly infectious and probable escape mutant. Considering the possible immune escape, we had already evaluated the efficacy of the BBV152 against Delta and Delta AY.1 variants. Here, we have evaluated the neutralizing potential of sera of COVID-19 naive vaccinees (CNV) immunized with two doses of vaccine, COVID-19 recovered cases immunized with two doses of vaccine (CRV) and breakthrough infections (BTI) post immunization with two doses of vaccine against Delta, Delta AY.1 and B.1.617.3 using 50% plaque reduction neutralization test (PRNT50). Our study observed low NAb titer in CNV group against all the variants compared to CRV and BTI groups. Delta variant has shown highest reduction of 27.3-fold in NAb titer among CNV group compared to other groups and variants. Anti-S1-RBD IgG immune response among all the groups was also substantiated with NAb response. Compromised neutralization was observed against Delta and Delta AY.1 compared B.1 in all three groups. However, it provided protection against severity of the disease and fatality.

https://biorxiv.org/content/10.1101/2021.11.30.470521v1.full.pdf

SARS-CoV-2 Delta derivatives impact on neutralization of Covishield recipient sera

Background & objectives: Nipah virus (NiV) is a zoonotic paramyxovirus that causes fatal encephalitis in humans. Enzyme Linked Immunosorbent Assay (ELISA) is a safe, sensitive, specific, and affordable diagnostic tool that can be used during screening of large-scale epidemiological investigations. Development and evaluation of IgM and IgG ELISA for screening serum samples of NiV suspected cases would also help in planning public health interventions. Methods: An IgM capture (MAC) ELISA and an indirect IgG ELISA were developed using NiV antigen to detect IgM and IgG antibodies against NiV in human sera. The sensitivity, specificity, and cross-reactivity of the assays were evaluated using NiV IgM, IgG positive, negative human sera and measles, mumps, rubella, Crimean-Congo haemorrhagic fever, Kyasanur forest disease IgM, IgG positive sera, respectively. Results: The developed anti-NiV IgM and IgG ELISAs have shown specificity of 99.28 per cent and sensitivity of 100 per cent compared to reference test from Centers for Disease Control and Prevention, USA. Assays demonstrated negative predictive value of 100 per cent and positive predictive value as 90 and 93.94 per cent for anti-Nipah IgM ELISA and IgG ELISA respectively with test accuracy of 99.33 per cent. Interpretation & conclusions: Timely diagnosis of NiV is crucial for the management of cases, which could prevent further spread of infection in the community. IgM ELISA can be used as primary diagnostic tool followed by polymerase chain reaction. These assays have advantages of its applicability during outbreak investigations and surveillance activities at hospital or onsite laboratories with basic biosafety practices.

https://doi.org/10.4103/ijmr.ijmr_2737_21

Pragya D Yadav

Papers

SARS-CoV-2 Delta derivatives impact on neutralization of Covishield recipient sera

Development of Nipah virus-specific IgM & IgG ELISA for screening human serum samples