Abstract
Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.
| Original language | English |
|---|---|
| Article number | e29591 |
| Number of pages | 16 |
| Journal | Heliyon |
| Volume | 10 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 30 May 2024 |
| Externally published | Yes |
Keywords
- COVID-19
- Mortality
- Non-respiratory symptoms
- Respiratory symptoms
- Risk factors
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In: Heliyon, Vol. 10, No. 10, e29591, 30.05.2024.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms
AU - Citarella, Barbara Wanjiru
AU - Kartsonaki, Christiana
AU - Ibáñez-Prada, Elsa D.
AU - Gonçalves, Bronner P.
AU - Baruch, Joaquin
AU - Escher, Martina
AU - Pritchard, Mark G.
AU - Wei, Jia
AU - Philippy, Fred
AU - Dagens, Andrew
AU - Hall, Matthew
AU - Lee, James
AU - Kutsogiannis, Demetrios James
AU - Wils, Evert Jan
AU - Fernandes, Marília Andreia
AU - Tirupakuzhi Vijayaraghavan, Bharath Kumar
AU - Panda, Prasan Kumar
AU - Martin-Loeches, Ignacio
AU - Ohshimo, Shinichiro
AU - Fatoni, Arie Zainul
AU - Horby, Peter
AU - Dunning, Jake
AU - Rello, Jordi
AU - Merson, Laura
AU - Rojek, Amanda
AU - Vaillant, Michel
AU - Olliaro, Piero
AU - Reyes, Luis Felipe
AU - Moharam, S. A.
AU - Abdalasalam, Sabriya
AU - Abdalhadi, Alaa Abdalfattah
AU - Abdalla, Naana Reyam
AU - Abdalla, Walaa
AU - Abdalrheem, Almthani Hamza
AU - Abdalsalam, Ashraf
AU - Abdeewi, Saedah
AU - Abdelgaum, Esraa Hassan
AU - Abdelhalim, Mohamed
AU - Abdelkabir, Mohammed
AU - Abdelrahman, Israa
AU - Abdukahil, Sheryl Ann
AU - Abdulbaqi, Lamees Adil
AU - Abdulhamid, Salaheddin
AU - Abdulhamid, Widyan
AU - Abdulkadir, Nurul Najmee
AU - Abdulwahed, Eman
AU - Abdunabi, Rawad
AU - Abe, Ryuzo
AU - Abel, Laurent
AU - Abodina, Ahmed Mohammed
AU - Abrous, Amal
AU - Absil, Lara
AU - Jabal, Kamal Abu
AU - Salah, Nashat Abu
AU - Abusalama, Abdurraouf
AU - Abuzaid, Tareg Abdallah
AU - Acharya, Subhash
AU - Acker, Andrew
AU - Adam, Elisabeth
AU - Adem, Safia
AU - Ademnou, Manuella
AU - Adewhajah, Francisca
AU - Adrião, Diana
AU - Afum-Adjei Awuah, Anthony
AU - Agbogbatey, Melvin
AU - Al Ageel, Saleh
AU - Ahmed, Aya Mustafa
AU - Ahmed, Musaab Mohammed
AU - Ahmed, Shakeel
AU - Alaraji, Zainab Ahmed
AU - Elhefnawy Enan, Abdulrahman Ahmed
AU - Ahmed Khalil, Reham Abdelhamid
AU - Ahmed Mohamed Abdelaziz, Ali Mostafa
AU - Ainscough, Kate
AU - Airlangga, Eka
AU - Aisa, Tharwat
AU - Aisha, Ali
AU - Aisha, Bugila
AU - Hssain, Ali Ait
AU - Tamlihat, Younes Ait
AU - Akimoto, Takako
AU - Akmal, Ernita
AU - Akwani, Chika
AU - Al Qasim, Eman
AU - Alajeeli, Ahmed
AU - Alali, Ahmed
AU - Alalqam, Razi
AU - Alameen, Aliya Mohammed
AU - Al-Aquily, Mohammed
AU - Alaraji, Zinah A.
AU - Albakry, Khalid
AU - Albatni, Safa
AU - Alberti, Angela
AU - Aldabbourosama, Osama
AU - Al-dabbous, Tala
AU - Aldhalia, Amer
AU - Aldoukali, Abdulkarim
AU - Alegesan, Senthilkumar
AU - Alessi, Marta
AU - Alex, Beatrice
AU - Alexandre, Kévin
AU - Al-Fares, Abdulrahman
AU - Alflite, Asil
AU - Alfoudri, Huda
AU - Alhadad, Qamrah
AU - Alhaddad, Hoda Salem
AU - Mohamed Abdalla Alhasan, Maali Khalid
AU - Alhouri, Ahmad Nabil
AU - Alhouri, Hasan
AU - Ali, Adam
AU - Ali, Imran
AU - TagElser Mohammed Ali, Maha
AU - Abbas, Syed Ali
AU - Abdelghafar, Yomna Ali
AU - Sheikh, Naseem Ali
AU - Alidjnou, Kazali Enagnon
AU - Aljadi, Mahmoud
AU - Aljamal, Sarah
AU - Alkahlout, Mohammed
AU - Alkaseek, Akram
AU - Alkhafajee, Qabas
AU - Allavena, Clotilde
AU - Allou, Nathalie
AU - Almasri, Lana
AU - Almjersah, Abdulrahman
AU - Alqandouz, Raja Ahmed
AU - Alrfaea, Walaa
AU - Alrifaee, Moayad
AU - Alsaadi, Rawan
AU - Al-Saba'a, Yousef
AU - Alshareea, Entisar
AU - Alshenawy, Eslam
AU - Altaf, Aneela
AU - Alves, João
AU - Alves, João
AU - Alves, Rita
AU - Cabrita, Joana Alves
AU - Amaral, Maria
AU - Amer, Amro Essam
AU - Amira, Nur
AU - Adusei, Amos Amoako
AU - Amuasi, John
AU - Andini, Roberto
AU - Andrejak, Claire
AU - Angheben, Andrea
AU - Angoulvant, François
AU - Ankrah, Sophia
AU - Ansart, Séverine
AU - Anthonidass, Sivanesen
AU - Antonelli, Massimo
AU - Antunes de Brito, Carlos Alexandre
AU - Apriyana, Ardiyan
AU - Arabi, Yaseen
AU - Aragao, Irene
AU - Arancibia, Francisco
AU - Araujo, Carolline
AU - Arcadipane, Antonio
AU - Archambault, Patrick
AU - Arenz, Lukas
AU - Arlet, Jean Benoît
AU - Arnold-Day, Christel
AU - Arora, Lovkesh
AU - Arora, Rakesh
AU - Artaud-Macari, Elise
AU - Aryal, Diptesh
AU - Asensio, Angel
AU - Ashley, Elizabeth A.
AU - Ashraf, Muhammad
AU - Ashraf, Muhammad Sheharyar
AU - Ben Ashur, Abir
AU - Asiedu-Bekoe, Franklin
AU - Asif, Namra
AU - Asim, Mohammad
AU - Assi, Grace
AU - Assie, Jean Baptiste
AU - Asyraf, Amirul
AU - Atangana, Fouda
AU - Atia, Ahmed
AU - Atif, Minahel
AU - Abdelrhman Abdallahrs, Asia Atif
AU - Atique, Anika
AU - Atlowly, Moad
AU - Attanyake, AM Udara Lakshan
AU - Auchabie, Johann
AU - Aumaitre, Hugues
AU - Auvet, Adrien
AU - Ali Mohammed, Abdelmalek Awad
AU - Axelsen, Eyvind W.
AU - Ayad, Ared
AU - Hassan Helmi, Ahmed Ayman
AU - Azemar, Laurène
AU - Azizeldin, Mohammed
AU - Azoulay, Cecile
AU - Babatunde, Hakeem
AU - Bach, Benjamin
AU - Bachelet, Delphine
AU - Badr, Claudine
AU - Bævre-Jensen, Roar
AU - Baig, Nadia
AU - Baillie, John Kenneth
AU - Baird, J. Kevin
AU - Bak, Erica
AU - Bakakos, Agamemnon
AU - Bakar, Nazreen Abu
AU - Bakeer, Hibah Bileid
AU - Bakri, Ashraf
AU - Bal, Andriy
AU - Balakrishnan, Mohanaprasanth
AU - Bandoh, Irene
AU - Bani-Sadr, Firouzé
AU - Barbalho, Renata
AU - Barbosa, Nicholas Yuri
AU - Barclay, Wendy S.
AU - Barnett, Saef Umar
AU - Barnikel, Michaela
AU - Barrasa, Helena
AU - Barrigoto, Cleide
AU - Bartoli, Marie
AU - Baruch, Joaquín
AU - Basmaci, Romain
AU - Basri, Muhammad Fadhli Hassin
AU - Batool, Abd Alkarim
AU - Battaglini, Denise
AU - Bauer, Jules
AU - Bautista Rincon, Diego Fernando
AU - Dow, Denisse Bazan
AU - Beane, Abigail
AU - Bedossa, Alexandra
AU - Bee, Ker Hong
AU - Begum, Husna
AU - Behilill, Sylvie
AU - Beishuizen, Albertus
AU - Beljantsev, Aleksandr
AU - Bellemare, David
AU - Beltrame, Anna
AU - Beltrão, Beatriz Amorim
AU - Beluze, Marine
AU - Benech, Nicolas
AU - Benjiman, Lionel Eric
AU - Brewster, David
AU - Broadley, Tessa
AU - Fraser, John F.
AU - French, Craig
AU - Nichol, Alistair D.
AU - Parke, Rachael
AU - Peake, Sandra L.
AU - Trapani, Tony
AU - Udy, Andrew
AU - Webb, Steve
AU - Williams, Patricia J.
AU - ISARIC Clinical Characterisation Group
N1 - Funding Information: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z and 220757/Z/20/Z]; the Bill & Melinda Gates Foundation [OPP1209135]; the philanthropic support of the donors to the University of Oxford's COVID-19 Research Response Fund (0009109); grants from the National Institute for Health Research (NIHR; award CO\u2013CIN-01/DH_/Department of Health/United Kingdom), the Medical Research Council (MRC; grant MC_PC_19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award ISBRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support; Cambridge NIHR Biomedical Research Centre (award NIHR203312); funding from Medical Research Council (UK Research and Innovation; award number MC_PC_19084) and Medical Research Council (MC_UU_00031/7); the Comprehensive Local Research Networks (CLRNs) of which PJMO is an NIHR Senior Investigator (NIHR201385); CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and the coordination in Canada by Sunnybrook Research Institute; funding by the Health Research Board of Ireland [CTN-2014-12]; the Rapid European COVID-19 Emergency Response research (RECOVER) [H2020 project 101003589] and European Clinical Research Alliance on Infectious Diseases (ECRAID) [965313]; a Research Council of Norway grant no 312780, and a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner; the South Eastern Norway Health Authority and the Research Council of Norway; Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115523 COMBACTE, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007\u20132013) and EFPIA companies, in-kind contribution; the French COVID cohort (NCT04262921) is sponsored by INSERM and is funded by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n\u00B020\u20130424); Stiftungsfonds zur F\u00F6rderung der Bek\u00E4mpfung der Tuberkulose und anderer Lungenkrankheiten of the City of Vienna, Project Number: APCOV22BGM; funding from Medical University of Vienna, Department of Anaesthesia, Intensive Care Medicine and Pain Medicine; Italian Ministry of Health \u201CFondi Ricerca corrente\u2013L1P6\u201D to IRCCS Ospedale Sacro Cuore\u2013Don Calabria; Australian Department of Health grant (3273191); Gender Equity Strategic Fund at University of Queensland, Artificial Intelligence for Pandemics (A14PAN) at University of Queensland, the Australian Research Council Centre of Excellence for Engineered Quantum Systems (EQUS, CE170100009), the Prince Charles Hospital Foundation, Australia; Australian Department of Health grant (3273191); Brazil, National Council for Scientific and Technological Development Scholarship number 303953/2018- 7; the Firland Foundation, Shoreline, Washington, USA; a grant from foundation Bevordering Onderzoek Franciscus; a grant from foundation Bevordering Onderzoek Franciscus; Institute for Clinical Research (ICR), National Institutes of Health (NIH) supported by the Ministry of Health Malaysia; funding from Saisei Mirai/Saisei Pharma, Japan; the U.S. DoD Armed Forces Health Surveillance Division, Global Emerging Infectious Diseases Branch to the U.S Naval Medical Research Unit No. TWO (NAMRU-2) (Work Unit #: P0153_21_N2). These authors would like to thank Vysnova Partners, Inc. for the management of this research project. The Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit is funded by the Wellcome Trust.The investigators acknowledge the support of the COVID clinical management team, AIIMS, Rishikesh, India; the COVID-19 Clinical Management team, Manipal Hospital Whitefield, Bengaluru, India; the dedication and hard work of the Groote Schuur Hospital Covid ICU Team and supported by the Groote Schuur nursing and University of Cape Town registrar bodies coordinated by the Division of Critical Care at the University of Cape Town; the Liverpool School of Tropical Medicine and the University of Oxford; Imperial NIHR Biomedical Research Centre; the dedication and hard work of the Norwegian SARS-CoV-2 study team; endorsement of the Irish Critical Care- Clinical Trials Group, co-ordination in Ireland by the Irish Critical Care- Clinical Trials Network at University College Dublin; the hard work and dedication of clinical, laboratory, research and support staff at EFSTH and MRCG; and preparedness work conducted by the Short Period Incidence Study of Severe Acute Respiratory Infection. This work uses data provided by patients and collected by the NHS as part of their care and support #DataSavesLives. The data used for this research were obtained from ISARIC4C. We are extremely grateful to the 2648 frontline NHS clinical and research staff and volunteer medical students who collected these data in challenging circumstances; and the generosity of the patients and their families for their individual contributions in these difficult times. The COVID-19 Clinical Information Network (CO\u2013CIN) data was collated by ISARIC4C Investigators. We also acknowledge the support of Jeremy J Farrar and Nahoko Shindo. Funding Information: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z and 220757/Z/20/Z]; the Bill & Melinda Gates Foundation [OPP1209135]; the philanthropic support of the donors to the University of Oxford\u2019s COVID-19 Research Response Fund (0009109); grants from the National Institute for Health Research (NIHR; award CO-CIN-01/DH_/Department of Health/United Kingdom), the Medical Research Council (MRC; grant MC_PC_19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award ISBRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support; Cambridge NIHR Biomedical Research Centre (award NIHR203312); funding from Medical Research Council (UK Research and Innovation; award number MC_PC_19084) and Medical Research Council (MC_UU_00031/7); the Comprehensive Local Research Networks (CLRNs) of which PJMO is an NIHR Senior Investigator (NIHR201385); CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and the coordination in Canada by Sunnybrook Research Institute; funding by the Health Research Board of Ireland [CTN-2014-12]; the Rapid European COVID-19 Emergency Response research (RECOVER) [H2020 project 101003589] and European Clinical Research Alliance on Infectious Diseases (ECRAID) [965313]; a Research Council of Norway grant no 312780, and a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner; the South Eastern Norway Health Authority and the Research Council of Norway; Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115523 COMBACTE, resources of which are composed of financial contribution from the European Union\u2019s Seventh Framework Programme (FP7/2007- 2013) and EFPIA companies, in-kind contribution; the French COVID cohort (NCT04262921) is sponsored by INSERM and is funded by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n\u00B020-0424); Stiftungsfonds zur F\u00F6rderung der Bek\u00E4mpfung der Tuberkulose und anderer Lungenkrankheiten of the City of Vienna, Project Number: APCOV22BGM; funding from Medical University of Vienna, Department of Anaesthesia, Intensive Care Medicine and Pain Medicine; Italian Ministry of Health \u201CFondi Ricerca corrente\u2013L1P6\u201D to IRCCS Ospedale Sacro Cuore\u2013Don Calabria; Australian Department of Health grant (3273191); Gender Equity Strategic Fund at University of Queensland, Artificial Intelligence for Pandemics (A14PAN) at University of Queensland, the Australian Research Council Centre of Excellence for Engineered Quantum Systems (EQUS, CE170100009), the Prince Charles Hospital Foundation , Australia; Australian Department of Health grant (3273191); Brazil, National Council for Scientific and Technological Development Scholarship number 303953/2018- 7; the Firland Foundation, Shoreline, Washington, USA; a grant from foundation Bevordering Onderzoek Franciscus; a grant from foundation Bevordering Onderzoek Franciscus; Institute for Clinical Research (ICR), National Institutes of Health (NIH) supported by the Ministry of Health Malaysia; funding from Saisei Mirai/Saisei Pharma, Japan; the U.S. DoD Armed Forces Health Surveillance Division, Global Emerging Infectious Diseases Branch to the U.S Naval Medical Research Unit No. TWO (NAMRU-2) (Work Unit #: P0153_21_N2). These authors would like to thank Vysnova Partners, Inc. for the management of this research project. The Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit is funded by the Wellcome Trust. Funding Information: The investigators acknowledge the support of the COVID clinical management team, AIIMS, Rishikesh, India; the COVID-19 Clinical Management team, Manipal Hospital Whitefield, Bengaluru, India; the dedication and hard work of the Groote Schuur Hospital Covid ICU Team and supported by the Groote Schuur nursing and University of Cape Town registrar bodies coordinated by the Division of Critical Care at the University of Cape Town; the Liverpool School of Tropical Medicine and the University of Oxford; Imperial NIHR Biomedical Research Centre; the dedication and hard work of the Norwegian SARS-CoV-2 study team; endorsement of the Irish Critical Care- Clinical Trials Group, co-ordination in Ireland by the Irish Critical Care- Clinical Trials Network at University College Dublin; the hard work and dedication of clinical, laboratory, research and support staff at EFSTH and MRCG; and preparedness work conducted by the Short Period Incidence Study of Severe Acute Respiratory Infection. Publisher Copyright: © 2024 The Authors
PY - 2024/5/30
Y1 - 2024/5/30
N2 - Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.
AB - Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.
KW - COVID-19
KW - Mortality
KW - Non-respiratory symptoms
KW - Respiratory symptoms
KW - Risk factors
UR - http://www.scopus.com/inward/record.url?scp=85192803986&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2024.e29591
DO - 10.1016/j.heliyon.2024.e29591
M3 - Article
C2 - 38779000
AN - SCOPUS:85192803986
SN - 2405-8440
VL - 10
JO - Heliyon
JF - Heliyon
IS - 10
M1 - e29591
ER -