Immunological dysfunction persists 8 months from initial mild-moderate SARS-CoV-2 infection

  

View ORCID ProfileChansavath Phetsouphanh,  View ORCID ProfileDavid Darley, Daniel B Wilson, Annett Howe,  View ORCID ProfileC. Mee Ling Munier, Sheila K Patel,  View ORCID ProfileJennifer A Juno,  View ORCID ProfileLouise M Burrell, Stephen J Kent, Gregory J Dore, Anthony D Kelleher, Gail V Matthews

doi: https://doi.org/10.1101/2021.06.01.21257759

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.06.01.21257759v2.full.pdf

Abstract

A proportion of patients surviving acute COVID-19 infection develop post-COVID syndrome (long COVID) encompassing physical and neuropsychiatric symptoms lasting longer than 12 weeks. Here we studied a prospective cohort of individuals with long COVID compared to age/gender matched subjects without long COVID (from the ADAPT study), healthy donors and individuals infected with other non-SARS CoV2 human coronaviruses (the ADAPT-C study). We found highly activated innate immune cells and an absence of subsets of un-activated naïve T and B cells in peripheral blood of long COVID subjects, that did not reconstitute over time. These activated myeloid cells may contribute to the elevated levels of type I (IFN-β) and III interferon (IFN-λ1) that remained persistently high in long COVID subjects at 8 months post-infection. We found positive inter-analyte correlations that consisted of 18 inflammatory cytokines in symptomatic long COVID subjects that was not observed in asymptomatic COVID-19 survivors. A linear classification model was used to exhaustively search through all 20475 combinations of the 29 analytes measured, that had the strongest association with long COVID and found that the best 4 analytes were: IL-6, IFN-γ, MCP-1 (CCL2) and VCAM-1. These four inflammatory biomarkers gave an accuracy of 75.9%, and an F1 score of 0.759, and have also previously been associated with acute severe disease. In contrast, plasma ACE2 levels, while elevated in the serum of people previously infected with SARS-CoV-2 were not further elevated in subjects with long COVID symptoms. This work defines immunological parameters associated with long COVID and suggests future opportunities to prevention and treatment.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

ACTRN12620000554965

Funding Statement

We appreciate grant support from the St Vincents Clinic Foundation - the Curran Foundation, the Rapid Response Research Fund (UNSW) - the Medical Research Futures Fund (Australia) - NHMRC programme grant APP 1055214 (LMB) - Medical Research Future Fund award GNT 1175865 - - Austin Medical Research Foundation Grant - the Victorian Government - MRFF Award (2005544) - NHMRC program grant (1149990) - NHMRC Fellowships 1136322 and 1123673

https://www.medrxiv.org/content/10.1101/2021.06.01.21257759v2

Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces

 Shanna Ratnesar-Shumate, Gregory Williams, Brian Green, Melissa Krause, Brian Holland, Stewart Wood, Jordan Bohannon, Jeremy Boydston, Denise Freeburger, Idris Hooper ...

DOI: https://doi.org/10.1093/infdis/jiaa274

PDF: https://academic.oup.com/jid/article-pdf/222/2/214/33441804/jiaa274.pdf

Abstract

Previous studies have demonstrated that SARS-CoV-2 is stable on surfaces for extended periods under indoor conditions. In the present study, simulated sunlight rapidly inactivated SARS-CoV-2 suspended in either simulated saliva or culture media and dried on stainless steel coupons. Ninety percent of infectious virus was inactivated every 6.8 minutes in simulated saliva and every 14.3 minutes in culture media when exposed to simulated sunlight representative of the summer solstice at 40°N latitude at sea level on a clear day. Significant inactivation also occurred, albeit at a slower rate, under lower simulated sunlight levels. The present study provides the first evidence that sunlight may rapidly inactivate SARS-CoV-2 on surfaces, suggesting that persistence, and subsequently exposure risk, may vary significantly between indoor and outdoor environments. Additionally, these data indicate that natural sunlight may be effective as a disinfectant for contaminated nonporous materials.

https://academic.oup.com/jid/article/222/2/214/5841129

High failure rate of ChAdOx1 in health workers in Delta surge: Case for continued mask use

 Rajat Ujjainiya, Akansha Tyagi,  

View ORCID ProfileViren Sardana, Salwa Naushin, Nitin Bhatheja, Kartik Kumar, Joydeb Barman, Satyartha Prakash, Rintu Kutum, Akash K Bhaskar, Prateek Singh, Kumardeep Chaudhary, Menka Loomba, Yukti Khanna, Chestha Walecha, Rizwan Ahmed, Ashutosh Yadav, Archana Bajaj, Gaurav Malik, Sahar Qureshi, Swati Waghdhare, Samreen Siddiqui, Kamal Krishan Trehan, Manju Mani, Rajiv Dang, Poonam Das, Pankaj Dougall, Monica Mahajan, Sudipta Sonar, Kamini Jakhar, Reema Kumar, Mahima Tiwari, Shailendra Mani,  View ORCID ProfileSankar Bhattacharyya, Sandeep Budhiraja, Anurag Agrawal, Debasis Dash, Sujeet Jha, Shantanu Sengupta

doi: https://doi.org/10.1101/2021.02.28.21252621

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.02.28.21252621v5.full.pdf

Abstract

Immunization is expected to confer protection against infection and severe disease for vaccinees, while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies, we show that during a severe SARS-CoV2 Delta-variant outbreak in Delhi, 25.3% (95% CI 16.9 - 35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare-workers (HCW) were infected within a period of less than two months, based on serology. Induction of anti-spike response was similar between groups with breakthrough infection (541 U/ml, IQR 374) or not (342 U/ml, IQR 497), as was induction of neutralization activity to wildtype. Most infections were unrecognized. The Delta-variant thus causes frequent unrecognized breakthrough infections in adequately immunized subjects, reducing any herd-effect of immunity, and requiring reinstatement of preventive measures such as masking.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

SSG would like to acknowledge CSIR grant MLP 2007 for this work. The sponsor of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

https://www.medrxiv.org/content/10.1101/2021.02.28.21252621v5

Fully vaccinated can carry as much delta virus as unvaccinated people, data indicate

 Shaun Griffin

doi: https://doi.org/10.1136/bmj.n2074

PDF: https://www.bmj.com/content/374/bmj.n2074.full.pdf

Adults who have been fully vaccinated against SARS-CoV-2 can carry the same viral load of the delta variant as those who are unvaccinated, a preliminary analysis of UK data suggests.1

The latest results from the UK’s national covid-19 infection survey show that having two vaccine doses remains the most effective way to ensure protection against delta. But, although people who are fully vaccinated have a lower risk of becoming infected, those infected with the delta variant can carry similar virus levels as unvaccinated people, the data show. The authors said the implications for transmission were not yet clear but suggested that the potential for fully vaccinated individuals to transmit the virus to others would make achieving herd immunity more of a challenge.

Sarah Walker, professor of medical statistics and epidemiology at the University of Oxford and chief investigator of the survey, said, “We don’t yet know how much transmission can happen from people who get covid-19 after being vaccinated—for example, they may have high levels of virus for shorter periods of time.

“But the fact that they can have high levels of virus suggests that people who aren’t yet vaccinated may not be as protected from the delta variant as we hoped. This means it is essential for as many people as possible to get vaccinated—both in the UK and worldwide.”

The analysis, published as a preprint and not yet peer reviewed, found that the Oxford-AstraZeneca and Pfizer-BioNTech vaccines both offered good protection against new infections but that performance was less good against delta than with the previously dominant alpha variant.

The researchers analysed 2 580 021 results from swabs taken from 384 543 adults between 1 December 2020 and 16 May 2021, when the alpha variant predominated, and 811 624 results from 358 983 adults between 17 May and 1 August 2021, when delta prevailed. Two doses of either vaccine provided at least the same level of protection as that afforded through natural infection with the virus. For example, when delta prevailed, efficacy of the Pfizer vaccine was 80% (95% confidence interval 77% to 83%) at 14 or more days after two doses, higher than after two doses of the AstraZeneca vaccine (67% (62% to 71%)) but not significantly different from the protection afforded by natural immunity in non-vaccinated people who had tested positive for SARS-CoV-2 (72% (58% to 82%)).

The effectiveness of the two vaccines did not depend on the time between first and second doses. But people who were vaccinated after they had had covid-19 had more protection from vaccination than those who were vaccinated without a previous natural infection. For example, 14 days after a second AstraZeneca dose, on average the rates of all new covid-19 infections had dropped by 88% among those with prior infection, which compared with 68% in those without prior infection. The percentages were 93% and 85%, respectively, for the Pfizer vaccine.

Speaking at a Science Media Centre briefing, Koen Pouwels, of Oxford University’s Nuffield Department of Population Health and the report’s lead author, emphasised the protective effect of vaccination in people with a high SARS-CoV-2 viral burden. He said that vaccine protection was 90% higher than in unvaccinated people one month after a second Pfizer vaccine, declining to 85% after two months and 78% after three months. For the AstraZeneca vaccine the equivalent protection was 67%, 65%, and 61%, respectively.

“Even with these slight declines in protection against all infections and infections with high viral burden, it’s important to note that overall effectiveness is still very high, because we were starting at such a high level of protection,” Pouwels said.

The study also showed that viral burden was lower immediately after two Pfizer doses but that it increased faster with time than after the AstraZeneca vaccine, leading to similar levels of viral burden around three months after second doses of both vaccines.

Commenting on the findings, the University of East Anglia’s Paul Hunter noted, “There is now quite a lot of evidence that all vaccines are much better at reducing the risk of severe disease than they are at reducing the risk from infection. We now know that vaccination will not stop infection and transmission, [but it does] reduce the risk. The main value of immunisation is in reducing the risk of severe disease and death.”

https://www.bmj.com/content/374/bmj.n2074.full