Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity

Young, Barnaby Edward; Ong, Sean Wei Xiang; Ng, Lisa F. P.; Anderson, Danielle E.; Chia, Wan Ni; Chia, Po Ying; Ang, Li Wei; Mak, Tze Minn; Kalimuddin, Shirin; Chai, Louis Yi Ann; Pada, Surinder; Tan, Seow Yen; Sun, Louisa; Parthasarathy, Purnima; Fong, Siew‐Wai; Chan, Yi‐Hao; Tan, Chee Wah; Lee, Bernett; Rötzschke, Olaf; Ding, Ying; Tambyah, Paul A.; Low, Jenny Guek Hong; Cui, Lin; Barkham, Timothy; Lin, Raymond Tzer Pin; Leo, Yee‐Sin; Rénia, Laurent; Wang, Lin‐Fa; Lye, David C.; Lim, Poh Lian; Ang, Brenda; Lee, Cheng Chuan; Lee, Lawrence S.; L, Li; Ng, Oon Tek; Chan, Mónica; Marimuthu, Kalisvar; Vasoo, Shawn; Wong, Chen Seong; Lee, Tau Hong; Sadarangani, Sapna; Lin, Ray Junhao; Sadasiv, Mucheli Sharavan; Ng, Deborah Hee Ling; Choy, Chiaw Yee; Tan, Glorijoy Shi En; Tan, Yu Kit; Sutjipto, Stephanie; Lee, Pei Hua; Tay, Jun Yang; Yeo, Tsin Wen; Khoo, Bo Yan; Tay, Woo Chiao; Ng, Gabrielle; Mah, Yun Yuan; Tan, Wilnard; De, Partha Pratim; Rao, Pooja; Chia, Jonathan W Z; Chen, Yuan Yi Constance; Mendis, Shehara; Toh, Boon Kiat; Fong, Raymond Kok Choon; Oh, H. M. L.; Chien, Jaime Mei Fong; Shafi, Humaira; Cheong, Hau Yiang; Tan, Thean Yen; Tan, Thuan Tong; Tan, Ban Hock; Wijaya, Limin; Venkatachalam, Indumathi; Chua, Ying Ying; Cherng, Benjamin Pei Zhi; Chan, Yvonne; Wong, Hei Man; Thien, Siew Yee; Goh, Kenneth Choon Meng; Tan, Sue Yee; Oon, Lynette Lin Ean; Chan, Kian Sing; Li, Lin; Chan, Douglas; Ooi, Say Tat; Narayana, Deepak Rama; Somani, Jyoti; Oon, Jolene; Yan, Gabriel; Allen, David Michael; Jureen, Roland; Yan, Benedict; Foo, Randy; Kang, Adrian Eng Zheng; Sivalingam, Velraj; How, Wilson; Fernandez, Norman Leo; Yeo, Nicholas Kim‐Wah; Chee, Rhonda Sin‐Ling; Amrun, Siti Naqiah

doi:10.1093/cid/ciaa1280

Cited by 174 publications

(191 citation statements)

References 38 publications

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“…In the study cohorts, a signi cant change was observed in plasma IL-6 in severe fatal cases (p = 0.0348, healthy vs. severe fatal case [early phase]; p = 0.0234, mild case vs. severe fatal case [early phase]) in line with previous studies in which IL-6 levels tended to be higher in severe cases (Fig. 3a) 14,15,24,25 . We also observed a signi cant and selective increase in IL-8 levels in the early and late phases of severe cases (p = 0.0004, healthy vs. severe surviving case [early phase]; p = 0.0002, mild vs. severe surviving case [early phase]; p = 0.0014, moderate I vs. severe surviving case [early phase]; p = 0.0001, moderate II vs. severe surviving case [early phase]; p = 0.0250, severe surviving case vs. severe fatal case [early phase]; p = 0.0388, moderate I vs. severe surviving case [late phase]; p = 0.0396, moderate II vs. severe surviving case [late phase]; Fig.…”

Section: Association Between Mdsc Subsets and Plasma Il-6 And Il-8 Lesupporting

confidence: 88%

Myeloid cell dynamics correlate with clinical outcomes of severe coronavirus disease 2019

Takano

Matsumoto

Adachi

et al. 2020

Preprint

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An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19); however, it remains unclear whether myeloid cells are beneficial or detrimental to the clinical outcome. Here, we tracked cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis by flow cytometric analysis of blood samples from COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, rather than other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Notably, this subset was selectively expanded in survivors of severe cases and diminished during recovery. Analysis of plasma cytokines/chemokines revealed that interleukin-8 increased prior to PMN-MDSC expansion in survivors and returned to basal levels during the recovery phase. In contrast, interleukin-6 and interferon--induced protein 10 were abundantly induced in non-survivors, suggesting possible downstream targets for the immunosuppressive effects of the MDSC subset. Our data indicate that increased cellularity of PMN-MDSCs might be beneficial for the clinical outcome and could be useful as a possible predictor of prognosis in cases of severe COVID-19.

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Section: Association Between Mdsc Subsets and Plasma Il-6 And Il-8 Lesupporting

confidence: 88%

Myeloid cell dynamics correlate with clinical outcomes of severe coronavirus disease 2019

Takano

Matsumoto

Adachi

et al. 2020

Preprint

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“…The latter would be consistent with the variable antibody responses now determined for the spectrum of pediatric disease [44]. For EIA-based antibody studies otherwise, we have learned so far that the type and severity of disease and age may have bearing on the quality and quantity of antibody responses [34,[45][46][47][48]. Gender may also possibly affect antibody responses or other relevant immune responses [34,49].…”

Section: Provisional Acceptance Of What Constitutes Immunitysupporting

confidence: 64%

A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

Cimolai

2020

SN Compr. Clin. Med.

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Until either efficacious therapy or vaccination for COVID-19 is achieved, there will be a need to regain world economic stability while yet controlling the pandemic with current approaches. For those infected thus far, there is a prevailing perspective that devising recognition for protective immunity will progressively allow segments of society to return to some functionality more than is existing. At this time, the best correlates with protection from natural coronavirus infections are systemic neutralizing antibody and mucosal IgA. Serum neutralizing antibody more easily fulfills the latter requisite, but current live virus methods for neutralization prevent large-scale application. It is conceivable that the exposure of previously infected individuals can allow for the definition of protective thresholds of neutralizing antibody. Thereafter, many other antibody assays will be able to screen for surrogate protection after correlations with protective neutralizing antibody are made. Specificity of common antibody tests would benefit from confirmatory blocking systems or confirmatory immunoblotting fingerprints with well-defined antigen(s). The opportunity for the scientific community to make these assessments is evident in the current context of the COVID-19 epidemic given the large numbers of infected individuals worldwide. Such information will also be vital to guide vaccine development and/or immunotherapy.

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“…[8,9] This may be accounted by rapid con rmatory diagnosis of SARS-CoV-2 infection as the cause of pneumonia in our setting, and the vast majority of patients having non-severe infections. [10] To prepare for the pandemic, the AMS team was requested by the hospital management to work with hospital pharmacy to provide recommendations on alternative antimicrobial use in anticipation of possible shortfall. In addition, the team briefed the hospital senior management on the possibilities of antibiotic supply disruption and shared on common inappropriate use that was previously observed during audit and feedback.…”

Section: Discussionmentioning

confidence: 99%

Effects of Coronavirus Disease 2019 (COVID-19) Pandemic on Antimicrobial Prevalence and Prescribing in a Tertiary Hospital in Singapore

Tan

Heng

et al. 2020

Preprint

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Background: The deployment of antimicrobial stewardship (AMS) teams to deal with the COVID-19 pandemic can lead to a loss of developed frameworks, best practices and leadership resulting in adverse impact on antimicrobial prescribing and resistance. We aim to investigate effects of reduction in AMS resources during the COVID-19 pandemic on antimicrobial prescribing and resistance.Methods: One of 5 full-time equivalent AMS pharmacists was deployed to support pandemic work and AMS rounds with infectious disease physicians were reduced from 5 to 2 times a week. A survey in acute inpatients was conducted using the Global Point Prevalence Survey methodology in July 2020 and compared with those in 2015 and 2017-2019.Results: The prevalence of antimicrobial prescribing (55% in 2015 to 49% in 2019 and 47% in 2020, p =0.02) and antibacterials (54% in 2015 to 45% in 2019 and 42% in 2020, p < 0.01) have been reducing despite the pandemic. Antimicrobial prescribing in infectious disease wards with suspected or confirmed COVID-19 cases was 29% in 2020. Overall, antimicrobial prescribing quality indicators continued to improve (e.g. reasons in notes, 91% in 2015 to 94% in 2019 and 97% in 2020, p <0.01) or remained stable (compliance to guideline, 71% in 2015 to 62% in 2019 and 73% in 2020, p =0.08). Conclusion: AMS efforts over the years paid dividends during the COVID-19 pandemic to sustain the control of antimicrobial prevalence and quality of AMU in non-COVID-19 wards and plausibly also in COVID-19 wards.

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Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity

Cited by 174 publications

References 38 publications

Myeloid cell dynamics correlate with clinical outcomes of severe coronavirus disease 2019

Myeloid cell dynamics correlate with clinical outcomes of severe coronavirus disease 2019

A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

Effects of Coronavirus Disease 2019 (COVID-19) Pandemic on Antimicrobial Prevalence and Prescribing in a Tertiary Hospital in Singapore

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