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2.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-338256

ABSTRACT

Omicron (B.1.1.529) shows extensive escape from vaccine immunity, although vaccination reduces severe disease and death1. Boosting with vaccines incorporating variant spike sequences could possibly broaden immunity2. One approach to choose the variant may be to measure immunity elicited by vaccination combined with variant infection. Here we investigated Omicron neutralization in people infected with the Beta (B.1.351) variant and subsequently vaccinated with Pfizer BNT162b2. We observed that Beta infection alone elicited poor Omicron cross-neutralization, similar to what we previously found3 with BNT162b2 vaccination alone or in combination with ancestral or Delta virus infection. In contrast, Beta infection combined with BNT162b2 vaccination elicited neutralization with substantially lower Omicron escape.

3.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333693

ABSTRACT

BACKGROUND: Pulse oximetry is used as an assessment tool to gauge the severity of COVID-19 infection and identify patients at risk of poor outcomes. 1,2,3,4 The pandemic highlights the need for accurate pulse oximetry, particularly at home, as infection rates increase in multiple global regions including the UK, USA and South Africa 5 . Over 100 million Samsung smartphones containing dedicated biosensors (Maxim Integrated Inc, San Jose, CA) and preloaded Apps to perform pulse oximetry, are in use globally. We performed detailed in human hypoxia testing on the Samsung S9 smartphone to determine if this integrated hardware meets full FDA/ISO requirements for clinical pulse oximetry. METHODS: The accuracy of integrated pulse oximetry in the Samsung 9 smartphone during stable arterial oxygen saturations (SaO 2 ) between 70% and 100% was evaluated in 12 healthy subjects. Inspired oxygen, nitrogen, and carbon dioxide partial pressures were monitored and adjusted via a partial rebreathing circuit to achieve stable target SaO 2 plateaus between 70% and 100%. Arterial blood samples were taken at each plateau and saturation measured on each blood sample using ABL-90FLEX blood gas analyzer. Bias, calculated from smartphone readings minus the corresponding arterial blood sample, was reported as root mean square deviation (RMSD). FINDINGS: The RMSD of the over 257 data points based on blood sample analysis obtained from 12 human volunteers tested was 2.6%. INTERPRETATION: Evaluation of the smartphone pulse oximeter performance is within requirements of <3.5% RMSD blood oxygen saturation (SpO 2 ) value for FDA/ISO clearance for clinical pulse oximetry. This is the first report of smartphone derived pulse oximetry measurements that meet full FDA/ISO accuracy certification requirements. Both Samsung S9 and S10 contain the same integrated pulse oximeter, thus over 100 million smartphones in current global circulation could be used to obtain clinically accurate spot SpO 2 measurements to support at home assessment of COVID-19 patients.

4.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-327015

ABSTRACT

Omicron has been shown to be highly transmissible and have extensive evasion of neutralizing antibody immunity elicited by vaccination and previous SARS-CoV-2 infection. Omicron infections are rapidly expanding worldwide often in the face of high levels of Delta infections. Here we characterized developing immunity to Omicron and investigated whether neutralizing immunity elicited by Omicron also enhances neutralizing immunity of the Delta variant. We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold. The increase in Delta variant neutralization in individuals infected with Omicron may result in decreased ability of Delta to re-infect those individuals. Along with emerging data indicating that Omicron, at this time in the pandemic, is less pathogenic than Delta, such an outcome may have positive implications in terms of decreasing the Covid-19 burden of severe disease.

5.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326997

ABSTRACT

The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron’s extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, crossrecognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.

6.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-325667

ABSTRACT

Omicron variant (B.1.1.529) infections are rapidly expanding worldwide, often in settings where the Delta variant (B.1.617.2) was dominant. We investigated whether neutralizing immunity elicited by Omicron infection would also neutralize the Delta variant and the role of prior vaccination. We enrolled 23 South African participants infected with Omicron a median of 5 days post-symptoms onset (study baseline) with a last follow-up sample taken a median of 23 days post-symptoms onset. Ten participants were breakthrough cases vaccinated with Pfizer BNT162b2 or Johnson and Johnson Ad26.CoV2.S. In vaccinated participants, neutralization of Omicron increased from a geometric mean titer (GMT) FRNT50 of 28 to 378 (13.7-fold). Unvaccinated participants had similar Omicron neutralization at baseline but increased from 26 to only 113 (4.4-fold) at follow-up. Delta virus neutralization increased from 129 to 790, (6.1-fold) in vaccinated but only 18 to 46 (2.5-fold, not statistically significant) in unvaccinated participants. Therefore, in Omicron infected vaccinated individuals, Delta neutralization was 2.1-fold higher at follow-up relative to Omicron. In a separate group previously infected with Delta, neutralization of Delta was 22.5-fold higher than Omicron. Based on relative neutralization levels, Omicron re-infection would be expected to be more likely than Delta in Delta infected individuals, and in Omicron infected individuals who are vaccinated. This may give Omicron an advantage over Delta which may lead to decreasing Delta infections in regions with high infection frequencies and high vaccine coverage.

8.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296585

ABSTRACT

Characterizing SARS-CoV-2 evolution in specific geographies may help predict the properties of variants coming from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from the ancestral virus in a person with advanced HIV disease. Infection was before the emergence of the Beta variant first identified in South Africa, and the Delta variant. We compared early and late evolved virus to the ancestral, Beta, Alpha, and Delta viruses and tested against convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, whereas late virus was similar to Beta, exhibiting vaccine escape and, despite pre-dating Delta, strong escape of Delta-elicited neutralization. This example is consistent with the notion that variants arising in immune-compromised hosts, including those with advanced HIV disease, may evolve immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections. Highlights: A prolonged ancestral SARS-CoV-2 infection pre-dating the emergence of Beta and Delta resulted in evolution of a Beta-like serological phenotypeSerological phenotype includes strong escape from Delta infection elicited immunity, intermediate escape from ancestral virus immunity, and weak escape from Beta immunityEvolved virus showed substantial but incomplete escape from antibodies elicited by BNT162b2 vaccination. Graphical abstract:

9.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-296584

ABSTRACT

The emergence of the SARS-CoV-2 Omicron variant, first identified in South Africa, may compromise the ability of vaccine and previous infection (1) elicited immunity to protect against new infection. Here we investigated whether Omicron escapes antibody neutralization elicited by the Pfizer BNT162b2 mRNA vaccine in people who were vaccinated only or vaccinated and previously infected. We also investigated whether the virus still requires binding to the ACE2 receptor to infect cells. We isolated and sequence confirmed live Omicron virus from an infected person in South Africa. We then compared neutralization of this virus relative to an ancestral SARS-CoV-2 strain with the D614G mutation. Neutralization was by blood plasma from South African BNT162b2 vaccinated individuals. We observed that Omicron still required the ACE2 receptor to infect but had extensive escape of Pfizer elicited neutralization. However, 5 out of 6 of the previously infected, Pfizer vaccinated individuals, all of them with high neutralization of D614G virus, showed residual neutralization at levels expected to confer protection from infection and severe disease (2). While vaccine effectiveness against Omicron is still to be determined, these data support the notion that high neutralization capacity elicited by a combination of infection and vaccination, and possibly by boosting, could maintain reasonable effectiveness against Omicron. If neutralization capacity is lower or wanes with time, protection against infection is likely to be low. However, protection against severe disease, requiring lower neutralization levels and involving T cell immunity, would likely be maintained.

10.
American Journal of Obstetrics and Gynecology ; 224(2):S490-S491, 2021.
Article in English | Web of Science | ID: covidwho-1140966
11.
American Journal of Gastroenterology ; 115(SUPPL):S1396, 2020.
Article in English | EMBASE | ID: covidwho-994485

ABSTRACT

INTRODUCTION: Acquired Hemophagocytic lymphohistiocytosis (HLH) is rare with an incidence of 1.2 per 1,000,000 individuals. It can be caused by infection, malignancy, autoimmune disorders or can be idiopathic. To our knowledge, we present the third case of a patient clinically diagnosed with HLH associated with isolated Hepatitis B. CASE DESCRIPTION/METHODS: A 49 year-old-male from Tajikistan with no past medical history presented with persistent fevers for 3 months associated with non-productive cough, unintentional weight loss and night sweats. Vitals were stable and physical exam was remarkable for pallor and hepatosplenomegaly. Labs: Hgb 7.8 g/dl, PLT 133 mcl, WBC 2.68 mcl, Ferritin 2717ng/ml, Triglycerides 421mg/dl. His pancytopenia was suggestive of an underlying hematological malignancy, and a bone marrow biopsy was performed;it was non-diagnostic, with minimal evidence of RBC phagocytosis. Extensive work up was obtained and negative (Figure 1). Serum soluble IL-2 level was elevated, 10972 units/mL. The patient was diagnosed with HLH secondary to chronic hepatitis B infection and treated with high dose dexamethasone, Etoposide and Tenofovir with significant improvement. DISCUSSION: HLH is a fatal, rare condition characterized by fever, hyperferritinemia, hepatosplenomegaly, hepatic dysfunction, and uncontrolled hemophagocytosis throughout the reticuloendothelial system caused by immune hyperactivation and hypercytokinemia. Acquired HLH is usually associated with malignancy, viral infection, autoimmune disorder, or can be idiopathic. Lymphoma is the most common malignancy to cause acquired HLH and Epstein-Barr virus the most common infection. Isolated Hepatitis B is an extremely rare cause of HLH, with 2 other cases reported. Despite having a non-diagnostic bone marrow biopsy, he met multiple diagnostic criteria for HLH;fever >7 days, splenomegaly, cytopenia involving >2 cell lines, hyperferritinemia, and elevated soluble interleukin-2. He was treated with Tenofovir, high-dose dexamethasone and Etoposide in order to prevent reactivation of Hepatitis B. This case highlights the urgency to establish the cause of HLH, with Hepatitis being a differential, as initiating chemotherapy without treating his Hepatitis B may have led to unwanted complications including delay in chemotherapy, hepatic failure, and death. HLH caused by isolated Hepatitis B is rare and this case serves to increase awareness of diagnosis and management, especially since there is now reported association with SARS-CoV-2 and HLH.

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