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"Convalescence"
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Recovery : the lost art of convalescence
Offers tools and wisdom for convalescence, and shows how tending to our bodies, environments, and perspectives can help us move through the landscape of illness--and come out the other side whole. -- Provided by publisher.
Book
Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase
Objective
This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase.
Methods
A retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-min walking distance (6MWD) and high resolution CT being collected at 30 days after discharged.
Results
Fifty-seven patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%,
p
= 0.019), higher lung total severity score (TSS) and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit.
Conclusion
Impaired diffusing-capacity, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.
Journal Article
A qualitative exploration of cardiovascular disease patients’ views and experiences with an eHealth cardiac rehabilitation intervention: The PATHway Project
The aim of this study is to explore participants' views and experiences of an eHealth phase 3 cardiac rehabilitation (CR) intervention: Physical Activity Towards Health (PATHway). Sixty participants took part in the PATHway intervention. Debriefs were conducted after the six-month intervention. All interviews were audio recorded and transcribed verbatim. Transcripts were analysed with Braun and Clarke's thematic analysis. Forty-four (71%) debriefs were conducted (n = 34 male, mean (SD) age 61 (10) years). Five key themes were identified: (1) Feedback on the components of the PATHway system, (2) Motivation, (3) Barriers to using PATHway, (4) Enablers to using PATHway, and (5) Post programme reflection. There were a number of subthemes within each theme, for example motivation explores participants motivation to take part in PATHway and participants motivation to sustain engagement with PATHway throughout the intervention period. Participant engagement with the components of the PATHway system was variable. Future research should focus on optimising participant familiarisation with eHealth systems and employ an iterative approach to development and evaluation.
Journal Article
SARS-CoV-2 Omicron Variant Neutralization in Serum from Vaccinated and Convalescent Persons
Serum from vaccinated persons was assayed for ability to neutralize the omicron variant of SARS-CoV-2. Persons who had received two doses of the BNT162b2, mRNA-1273, or ChAdOx1-S vaccine had serum that poorly neutralized omicron, but those who had recovered from infection and were then vaccinated or who had been vaccinated and had breakthrough infection had high levels of neutralizing activity.
Journal Article
T cell responses to SARS-CoV-2 spike cross-recognize Omicron
The SARS-CoV-2 Omicron variant (B.1.1.529) has multiple spike protein mutations
1
,
2
that contribute to viral escape from antibody neutralization
3
–
6
and reduce vaccine protection from infection
7
,
8
. 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. Here we assessed the ability of T cells to react to Omicron spike protein in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, or unvaccinated convalescent COVID-19 patients (
n
= 70). Between 70% and 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 for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (
n
= 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (
n
= 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. It remains to be determined whether well-preserved T cell immunity to Omicron contributes to protection from severe COVID-19 and is linked to early clinical observations from South Africa and elsewhere
9
–
12
.
T cell responses to spike protein from the SARS-CoV-2 Omicron variant (B.1.1.529) are broadly similar to the responses to ancestral, Beta (B.1.351) and Delta (B.1.617.2) spike protein in vaccinated, infected and unvaccinated individuals.
Journal Article
Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies
The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening
1
,
2
to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A–F)—a grouping that is highly concordant with knowledge-based structural classifications
3
–
5
. Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A–D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309)
6
and group F (for example, CR3022)
7
, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants.
A high-throughput yeast display platform is used to analyse the profiles of mutations in the SARS-CoV-2 receptor-binding domain (RBD) that enable escape from antibodies, and suggests that most anti-RBD antibodies can be escaped by the Omicron variant.
Journal Article
Considerable escape of SARS-CoV-2 Omicron to antibody neutralization
The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa
1
–
3
. It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike—located mostly in the N-terminal domain and the receptor-binding domain—that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development
4
, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose.
An isolate of the Omicron variant of SARS-COV-2 was completely or partially resistant to neutralization by all nine clinically approved monoclonal antibodies tested.
Journal Article
Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2
The B.1.1.529/Omicron variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally
1
. It is expected to become dominant in the coming weeks
2
, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations
3
that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies
4
. This concern is amplified by the findings of our study. Here we found that B.1.1.529 is markedly resistant to neutralization by serum not only from patients who recovered from COVID-19, but also from individuals who were vaccinated with one of the four widely used COVID-19 vaccines. Even serum from individuals who were vaccinated and received a booster dose of mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies against all known epitope clusters on the spike protein, we noted that the activity of 17 out of the 19 antibodies tested were either abolished or impaired, including ones that are currently authorized or approved for use in patients. Moreover, we also identified four new spike mutations (S371L, N440K, G446S and Q493R) that confer greater antibody resistance on B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.
The B.1.1.529/Omicron variant of SARS-CoV-2 is resistant to neutralization by serum not only from patients who recovered from COVID-19, but also from individuals vaccinated with one of the four widely used COVID-19 vaccines.
Journal Article
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
The recently emerged SARS-CoV-2 Omicron variant encodes 37 amino acid substitutions in the spike protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody-based therapeutics. Here we show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions in neutralizing activity were observed against Omicron compared to the ancestral pseudovirus in plasma from convalescent individuals and from individuals who had been vaccinated against SARS-CoV-2, but this loss was less pronounced after a third dose of vaccine. Most monoclonal antibodies that are directed against the receptor-binding motif lost in vitro neutralizing activity against Omicron, with only 3 out of 29 monoclonal antibodies retaining unaltered potency, including the ACE2-mimicking S2K146 antibody
1
. Furthermore, a fraction of broadly neutralizing sarbecovirus monoclonal antibodies neutralized Omicron through recognition of antigenic sites outside the receptor-binding motif, including sotrovimab
2
, S2X259
3
and S2H97
4
. The magnitude of Omicron-mediated immune evasion marks a major antigenic shift in SARS-CoV-2. Broadly neutralizing monoclonal antibodies that recognize RBD epitopes that are conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.
Pseudovirus assays and surface plasmon resonance show that the Omicron receptor-binding domain binds to human ACE2 with increased affinity relative to the ancestral virus, and that most neutralizing antibodies are considerably less potent against Omicron.
Journal Article