SARS-CoV-2 and COVID-19

This wiki is intended for healthcare professionals and should not be considered medical advice.

General
BMJ Best Practice: COVID-19 - expert advice contributions by Nick Beeching from Liverpool School of Hygiene and Tropical Medicine, Tom Fletcher and Robert Fowler : includes criteria/case definitions and treatment algorithm

This page by Nature curates key new research relevant to COVID-19

COVID-19 NICE guidelines and resources hub

Cennimo DJ, Bergman SJ and Olsen KM. (Updated 14 Jan 2021 when accessed 19 Jan) Coronavirus Disease 2019 (COVID-19). Medscape (website). Log-in required but free registration.

Prevention and Public Health
Haug, N., Geyrhofer, L., Londei, A. et al. Ranking the effectiveness of worldwide COVID-19 government interventions. Nat Hum Behav 4, 1303–1312 (2020). https://doi.org/10.1038/s41562-020-01009-0 Note the findings in Fig. 1

Auger KA, Shah SS, Richardson T, et al. Association Between Statewide School Closure and COVID-19 Incidence and Mortality in the US. JAMA. 2020;324(9):859–870. doi:10.1001/jama.2020.14348

van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020 Mar 17;382(16):1564–7.
 * Aerosol - up to 3 hours
 * Copper - 4 hours
 * Cardboard - 24 hours
 * Plastics, stainless steel - 72 hrs

Chan NC, Li K, Hirsh J. Peripheral Oxygen Saturation in Older Persons Wearing Nonmedical Face Masks in Community Settings. JAMA. 2020;324(22):2323–2324. doi:10.1001/jama.2020.21905

Stephen A. Lauer, Kyra H. Grantz, Qifang Bi, et al. TThe Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Intern Med.2020;172:577-582. [Epub ahead of print 10 March 2020]. doi:10.7326/M20-0504

Chu, Derek KChu, Derek K et al. (Jun 2020) Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis The Lancet, Volume 395, Issue 10242, 1973 - 1987

Contact tracing
John Hopkins online coursera course - COVID-19 Contact Tracing

PPE
CDC PPE FAQs

WHO - Personal protective equipment for COVID-19

BOHS, The Chartered Society for Worker Health Protection BOHS – Covid-19: Occupation Risk Rating and Control Options According to Exposure Rank July 2020

Transmission Dynamics
Cheng H, Jian S, Liu D, et al. (May 2020) Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset. JAMA Intern Med. 2020;180(9):1156–1163. doi:10.1001/jamainternmed.2020.2020

Shen Y, Li C, Dong H, et al. Community Outbreak Investigation of SARS-CoV-2 Transmission Among Bus Riders in Eastern China. JAMA Intern Med. 2020;180(12):1665–1671. doi:10.1001/jamainternmed.2020.5225

Pombal R, Hosegood I, Powell D. [https://jamanetwork.com/journals/jama/fullarticle/2771435. Risk of COVID-19 During Air Travel.] JAMA. 2020;324(17):1798. doi:10.1001/jama.2020.19108

Grijalva CG, Rolfes MA, Zhu Y, et al. Transmission of SARS-COV-2 Infections in Households — Tennessee and Wisconsin, April–September 2020. MMWR Morb Mortal Wkly Rep 2020;69:1631–1634. DOI: http://dx.doi.org/10.15585/mmwr.mm6944e1

Lee S, Kim T, Lee E, et al. Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea. JAMA Intern Med. 2020;180(11):1447–1452. doi:10.1001/jamainternmed.2020.3862

Herd Immunity
Omer SB, Yildirim I, Forman HP. Herd Immunity and Implications for SARS-CoV-2 Control. JAMA. 2020;324(20):2095–2096. doi:10.1001/jama.2020.20892

Aschwanden, C. (Oct 2020) The false promise of herd immunity for COVID-19. Nature News Feature. Nature 587, 26-28 (2020). doi: https://doi.org/10.1038/d41586-020-02948-4

Tobias S. Brett, Pejman Rohani (Oct 2020) Transmission dynamics reveal the impracticality of COVID-19 herd immunity strategies Proceedings of the National Academy of Sciences Oct 2020, 117 (41) 25897-25903; DOI: 10.1073/pnas.2008087117

Presentation and pathophysiology
Kumar R, Lee MH, Mickael C, et al. (Oct 2020) Pathophysiology and potential future therapeutic targets using preclinical models of COVID-19. ERJ Open Res. 2020;6(4):00405-2020. Published 2020 Dec 7. doi:10.1183/23120541.00405-2020

Varga, Zsuzsanna et al. Endothelial cell infection and endotheliitis in COVID-19 The Lancet, Volume 395, Issue 10234, 1417 - 1418 DOI: https://doi.org/10.1016/S0140-6736(20)30937-5

Garvin MR, Alvarez C, Miller JI, Prates ET, Walker AM, Amos BK, et al. A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm. van de Veerdonk FL, van der Meer JW, van de Veerdonk FL, Little R, editors. eLife. 2020 Jul 7;9:e59177.

Symptoms
COVID Symptom Study (17 July 2020) The COVID Symptom Study reveals six distinct ‘types’ of COVID-19. COVID Symptom Study/ZOE/KCL

Sudre C. H. et al. (16 June 2020) Symptom clusters in Covid19: A potential clinical prediction tool from the COVID Symptom study app. MedRxivdoi:https://doi.org/10.1101/2020.06.12.20129056

Gastroenterology
Yeoh YK, Zuo T, Lui GC, et al Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19 BMJ Gut. Published Online First: 11 January 2021. doi: 10.1136/gutjnl-2020-323020

Abstract

Objective Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.

Methods In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.

Results Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.

Conclusion Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.

Dermatology
Galván Casas, C. et al. (29 April 2020) Classification of the cutaneous manifestations of COVID‐19: a rapid prospective nationwide consensus study in Spain with 375 cases. British Journal of Dermatology 2020;183pg.71-77 doi: https://doi.org/10.1111/bjd.19163

Thrombo-embolic
Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med. 2020 Apr 28;382(20):e60.

Mental health in a pandemic
Taylor, S, Landry, CA, Paluszek, MM, Fergus, TA, McKay, D, Asmundson, GJG. COVID stress syndrome: Concept, structure, and correlates. Depression and Anxiety. 2020; 37: 706– 714. https://doi.org/10.1002/da.23071

Host
Pairo-Castineira, E., Clohisey, S., Klaric, L. et al. Genetic mechanisms of critical illness in Covid-19. Nature (2020). https://doi.org/10.1038/s41586-020-03065-y

Virus
Nextstrain.org SARS-CoV-2 genomic data (Global data)

Microreact SARS-CoV-2 genomic data visualisation (COG-UK)

The Danish mink strain
Lassaunière R. et al. (Nov 2020) Working paper on SARS-CoV-2 spike mutations arising in Danish mink, their spread to humans and neutralization data. From Statens Serum Institute

The UK strain Dec 2020 "VUI202012/01" B117
VUI - Variant Under Investigation

Russell P. (23 Dec 2020) New Variant of SARS-CoV-2 FAQs. Medscape UK.

Baker L. (19 Dec 2020) Independent SAGE scientists share update as new mutation triggers today’s lockdown announcements. Healthcare Newsdesk.

Twitter discussion(s) Dr Eric Feigl-Ding: B117 and ?decrease in Pfizer vaccine efficacy

"Omics" Resources
(pulled from this review):

SARS-CoV-2 Genome Sequencing Data, DNA Sequencing Data	https://www.ncbi.nlm.nih.gov/genbank/sars-cov-2-seqs/

SARS-CoV-2 Transcriptomic Map
 * RNA Sequencing Data	Open Science Framework: accession number doi:10.17605/OSF.IO/8F6N9


 * Kim, D et al. The Architecture of SARS-CoV-2 Transcriptome. Cell, Volume 181, Issue 4, 914 - 921.e10

SARS-CoV-2 and Human Protein Interactions, Mass Spectrometry Raw Data	http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD018117

SARS-CoV-2 Strains	https://nextstrain.org/ncov

Genomic Epidemiology   https://www.gisaid.org/

The COVID-19 Host Genetics Initiative, Host Genetics Data (GWAS, WES, WGS) https://www.covid19hg.org/

COVID-19 Cell Atlas, Single cell transcriptomics data	https://www.covid19cellatlas.org

Tests, viral persistence and immunity
Dan JM et al Immunological memory to SARS-CoV-2 assessed for greater than six months after infection. bioRxiv 2020.11.15.383323; doi: https://doi.org/10.1101/2020.11.15.383323

PCR
Lauren M. Kucirka, Stephen A. Lauer, Oliver Laeyendecker, et al. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure. Ann Intern Med.2020;173:262-267. [Epub ahead of print 13 May 2020]. doi:10.7326/M20-1495

Woloshin S, Patel N, Kesselheim AS. False Negative Tests for SARS-CoV-2 Infection — Challenges and Implications. New England Journal of Medicine. 2020 Aug 6;383(6):e38.

Isikbay M, Henry TS, Frank JA, Hope MD. When to rule out COVID-19: How many negative RT-PCR tests are needed? Respiratory Medicine Case Reports. 2020 Jan 1;31:101192.

Lateral flow tests
(8 Nov 2020) Preliminary report from the Joint PHE Porton Down & University of Oxford SARS-CoV-2 test development and validation cell: Rapid evaluation of Lateral Flow Viral Antigen detection devices (LFDs) for mass community testing Innova SARS-CoV-2 Antigen Rapid Qualitative Test
 * Specificity 99.68%; False positive rate 0.32% (0.06-0.39%)
 * Kit failure rates ranging from 0.65% to 16.8% with batch differences
 * 248/323 (76.8%) of the PCR positives are positive on lateral flow but also further data shows operator variation in performance
 * laboratory scientists (156/197 LFDs positive [79.2%, 95% CI: 72.8-84.6%])]
 * trained healthcare-workers (92/126 LFDs positive [73.0%, 95% CI: 64.3-80.5%])
 * self-trained members of the public given a protocol (214/372 LFDs positive [57.5%, 95% CI:52.3-62.6%]; p<0.0001 chi2(2)=30.1)

Antibodies and antibody testing
Deeks JJ.et al. (25 June 2020) [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013652/full '''Antibody tests for identification of current and past infection withSARS-CoV-2 (Review). Cochrane Database of Systematic Reviews'''], Issue 6. Art. No.: CD013652.doi: https://doi.org/10.1002/14651858.CD013652

Lisba Bastos M. et al. (1 July 2020) Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis. BMJ370:m2516 doi:https://doi.org/10.1136/bmj.m2516

Staines H. M. et al. (9 June 2020) Dynamics of IgG seroconversion and pathophysiology of COVID-19 infections. MedRxivdoi:https://doi.org/10.1101/2020.06.07.20124636

Choe PG, Kang CK, Suh HJ, Jung J, Song K-H, Bang JH, et al. Waning antibody responses in asymptomatic and symptomatic SARS-CoV-2 infection. Emerg Infect Dis. 2021 Jan [published online Dec 2020]. https://doi.org/10.3201/eid2701.203515

Viral shedding, live viral culture studies, persistence and reactivation
Gousseff M. et al. (Nov 2020) Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound? Journal of Infection, Volume 81, Issue 5, 2020, Pages 816-846, ISSN 0163-4453, https://doi.org/10.1016/j.jinf.2020.06.073.

[https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(20)30172-5/fulltext Lancet Review. SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis. Cevik et al. November 19, 2020] DOI:https://doi.org/10.1016/S2666-5247(20)30172-5 “Our findings suggest that, although patients with SARS-CoV-2 infection might have prolonged RNA shedding of up to 83 days in upper respiratory tract infection, no live virus was isolated from culture beyond day 9 of symptoms despite persistently high viral RNA loads."

[https://www.medrxiv.org/content/10.1101/2020.08.04.20167932v4 '''Viral cultures for COVID-19 infectivity assessment. Systematic review''' Tom Jefferson, Elizabeth Spencer, Jon Brassey, Carl Heneghan medRxiv 2020.08.04.20167932] doi: https://doi.org/10.1101/2020.08.04.20167932

[https://wwwnc.cdc.gov/eid/article/26/11/20-3219_article Perera R, Tso E, Tsang O, et al. SARS-CoV-2 Virus Culture and Subgenomic RNA for Respiratory Specimens from Patients with Mild Coronavirus Disease. Emerging Infectious Diseases. 2020;26(11):2701-2704.] doi:10.3201/eid2611.203219. Also see this news article which discusses the paper above: https://www.cidrap.umn.edu/news-perspective/2020/08/those-milder-covid-19-may-not-shed-live-virus-long

Roe, K. (2020), Explanation for COVID‐19 infection neurological damage and reactivations. Transbound Emerg Dis, 67: 1414-1415. https://doi.org/10.1111/tbed.13594

Dias De Melo et al. COVID-19-associated olfactory dysfunction reveals SARS-CoV-2 neuroinvasion and persistence in the olfactory system bioRxiv 2020.11.18.388819; doi: https://doi.org/10.1101/2020.11.18.388819

Gaebler et al. Evolution of Antibody Immunity to SARS-CoV-2 bioRxiv 2020.11.03.367391; doi: https://doi.org/10.1101/2020.11.03.367391 "Analysis of intestinal biopsies obtained from asymptomatic individuals 3 months after COVID-19 onset, using immunofluorescence, electron tomography or polymerase chain reaction, revealed persistence of SARS-CoV-2 in the small bowel of 7 out of 14 volunteers. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence."

T-cell evidence/Cellular immunity
Snyder et al. Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels medRxiv 2020.07.31.20165647; doi: https://doi.org/10.1101/2020.07.31.20165647 Also see NYTimes article (free but registration required) https://www.nytimes.com/2020/11/10/health/t-cell-test-coronavirus-immunity.html

Schwarzkopf S, Krawczyk A, Knop D, Klump H, Heinold A, Heinemann FM, et al. Cellular immunity in COVID-19 convalescents with PCR-confirmed infection but with undetectable SARS-CoV-2–specific IgG. Emerg Infect Dis. 2021 Jan [original pub date Oct 2020, cited Dec 2020]. https://doi.org/10.3201/eid2701.203772

Reinfection
Ju Zhang, Nan Ding, Lili Ren et al. COVID-19 reinfection in the presence of neutralizing antibodies National Science Review, 11 January 2021, nwab006, https://doi.org/10.1093/nsr/nwab006

Abstract In the face of the coronavirus disease 2019 (COVID-19), strong and long-lasting immunity is required to protect the host from secondary infections. Recent studies revealed potential inadequacy of antibodies against SARS-CoV-2 in some convalescent patients, raising serious concerns about COVID-19 reinfection. Here, from 273 COVID-19 patients, we identified six reinfections based on clinical, phylogenetic, virological, serological, and epidemiological data.

During the second episode, we observed re-emergence of COVID-19 symptoms, new pulmonary lesions on CT images, increased viral load, and secondary humoral immune responses. 'The interval between the two episodes ranged from 19 to 57 days, indicating COVID-19 reinfections could occur after a short recovery period in convalescent patients. More importantly, reinfection occurred not only in patients with inadequate immunity after the primary infection, but also in patients with measurable levels of neutralizing antibodies. This information will aid the implementation of appropriate public health and social measures to control COVID-19, as well as inform vaccine development.

Pregnancy and perinatal
Allotey John, Stallings Elena, Bonet Mercedes, Yap Magnus, Chatterjee Shaunak, Kew Tania et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis BMJ 2020; 370 :m3320

Vitamin D
Overall Vitamin D deficiency or insuffiency prevalence is high and vitamin D is a generally safe supplement (discussion on dose upper limits in literature below).

COVID-19
Jain, A., Chaurasia, R., Sengar, N.S. et al. Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep 10, 20191 (2020). https://doi.org/10.1038/s41598-020-77093-z

WHO/COVID-NMA VITAMIN D VS STANDARD CARE/PLACEBO - Tabular summary of vitamin D randomised controlled trials for COVID-19

Please note the expression of concern on the following article: Maghbooli Z, Sahraian MA, Ebrahimi M, Pazoki M, Kafan S, Tabriz HM, et al. (2020) Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection. PLoS ONE 15(9): e0239799. doi:10.1371/journal.pone.0239799

Martineau AR, Jolliffe DA, Hooper RL, et al. (Feb 2017) Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017;356:i6583. doi:10.1136/bmj.i6583

Upper limits
VitaminDWiki. Global Vitamin D recommendations - summer 2018 - A note on safe upper limits: There is not international consensus on the upper safe limit of Vitamin D, here it shows a summary of the different upper limits, with a general disagreement between placing it as 4,000 or 10,000 IU

Prevalence of insufficiency/deficiency
Joshua P. Sutherland, Ang Zhou, Matthew J. Leach, Elina Hyppönen. (Nov 2020) Differences and determinants of vitamin D deficiency among UK biobank participants: A cross-ethnic and socioeconomic study.C linical Nutrition, 2020, ISSN 0261-5614, https://doi.org/10.1016/j.clnu.2020.11.019.
 * "Asian ancestry (57.2% in winter/spring and 50.8% in summer/autumn) followed by those of Black African ancestry (38.5% and 30.8%, respectively), mixed (36.5%, 22.5%), Chinese (33.1%, 20.7%) and White European ancestry (17.5%, 5.9%)."
 * "Participants with higher socioeconomic deprivation were more likely to have 25(OH)D deficiency compared to less deprived participants (P = <1 × 10−300); this pattern was more apparent among those of White European ancestry and in summer (Pinteraction ≤6.4 × 10−5 for both)."
 * "outdoor-time in summer was less effective for Black Africans (OR 0.89, 95% CI 0.70, 1.12) than White Europeans (OR 0.40, 95% CI 0.38, 0.42)."

[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761874/ Hossein-nezhad, Arash, and Michael F Holick. “Vitamin D for health: a global perspective.” Mayo Clinic proceedings vol. 88,7 (2013): 720-55. doi:10.1016/j.mayocp.2013.05.011]
 * "It has been estimated that 20% to 80% of US, Canadian, and European men and women are vitamin D deficient"
 * " In the United States, vitamin D deficiency and insufficiency is estimated to be 27% to 91% in pregnant women [USA]... this rate is estimated to be 39% to 65% in Canada, 45% to 100% in Asia, 19% to 96% in Europe, and 25% to 87% in Australia and New Zealand"

RCTs
WHO/COVID-NMA consortium RCTs for pharmacologic treatments of COVID-19 with table of general characteristics of each trial, updated every Friday

Severity of COVID-19
Gupta S, Hayek SS, Wang W, et al. Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US. JAMA Intern Med. 2020;180(11):1436–1446. doi:10.1001/jamainternmed.2020.3596

Rodrigues TS et al. (cited Dec 2020) Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J Exp Med. 2021 Mar 1;218(3):e20201707. doi: 10.1084/jem.20201707. PMID: 33231615; PMCID: PMC7684031.

Obesity
Frasca et al. (Dec 2020) Effects of obesity on serum levels of SARS-CoV-2-specific antibodies in COVID-19 patients medRxiv 2020.12.18.20248483; doi: https://doi.org/10.1101/2020.12.18.20248483

Curtin, K.M., Pawloski, L.R., Mitchell, P. and Dunbar, J. (2020), COVID‐19 and Morbid Obesity: Associations and Consequences for Policy and Practice. World Medical & Health Policy, 12: 512-532. https://doi.org/10.1002/wmh3.361

Michaela R. Anderson, Joshua Geleris, David R. Anderson, et al. Body Mass Index and Risk for Intubation or Death in SARS-CoV-2 Infection: A Retrospective Cohort Study. Ann Intern Med.2020;173:782-790. [Epub ahead of print 29 July 2020]. doi:10.7326/M20-3214

Sara Y. Tartof, Lei Qian, Vennis Hong, et al. Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization. Ann Intern Med.2020;173:773-781. [Epub ahead of print 12 August 2020]. doi:10.7326/M20-3742

Gastroenterology and microbiome
Yeoh YK, Zuo T, Lui GC, et al Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19 BMJ Gut. Published Online First: 11 January 2021. doi: 10.1136/gutjnl-2020-323020

Abstract

Objective Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.

Methods In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.

Results Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.

Conclusion Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.