Stock Ticker

Acute SARS-CoV-2 infection | Nature Reviews Disease Primers

  • Chan, J. F.-W. et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 395, 514–523 (2020). An early report of the epidemiological, clinical and microbiological features of patients in a family cluster who became ill with an unexplained pneumonia, demonstrating person-to-person spread of a novel coronavirus.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhu, N. et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 382, 727–733 (2020). One of the first reports of SARS-CoV-2 identified in Wuhan, China, among hospitalized patients, with whole-genome sequencing, direct PCR and culture from bronchoalveolar lavage fluid confirming a novel type of coronavirus.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497–506 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • World Health Organization. Coronavirus Disease (COVID-19) Pandemic. WHO https://www.who.int/europe/emergencies/situations/covid-19 (2025).

  • Centers for Disease Control and Prevention. CDC Museum COVID-19 Timeline. CDC https://www.cdc.gov/museum/timeline/covid19.html (2023).

  • Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 5, 536 (2020).

    Article 

    Google Scholar
     

  • Zhou, P. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cao, C. et al. The architecture of the SARS-CoV-2 RNA genome inside virion. Nat. Commun. 12, 3917 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • World Health Organization. WHO COVID-19 dashboard. COVID-19 deaths. WHO https://data.who.int/dashboards/covid19/deaths?n=o (2025).

  • Bradshaw, D., Dorrington, R., Laubscher, R., Groenewald, P. & Moultrie, T. COVID-19 and all-cause mortality in South Africa — the hidden deaths in the first four waves. S. Afr. J. Sci. https://doi.org/10.17159/sajs.2022/13300 (2022).

  • Msemburi, W. et al. The WHO estimates of excess mortality associated with the COVID-19 pandemic. Nature 613, 130–137 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Starke, K. R. et al. The isolated effect of age on the risk of COVID-19 severe outcomes: a systematic review with meta-analysis. BMJ Glob. Health 6, e006434 (2021).

    Article 

    Google Scholar
     

  • Centers for Disease Control and Prevention. COVID-19 Provisional Counts – Weekly Updates by Select Demographic and Geographic Characteristics. CDC https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm (2023).

  • Scully, E. P., Haverfield, J., Ursin, R. L., Tannenbaum, C. & Klein, S. L. Considering how biological sex impacts immune responses and COVID-19 outcomes. Nat. Rev. Immunol. 20, 442–447 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dudley, J. P. & Lee, N. T. Disparities in age-specific morbidity and mortality from SARS-CoV-2 in China and the Republic of Korea. Clin. Infect. Dis. 71, 863–865 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Márquez, E. J. et al. Sexual-dimorphism in human immune system aging. Nat. Commun. 11, 751 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Piasecka, B. et al. Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges. Proc. Natl Acad. Sci. USA 115, E488–E497 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schurz, H. et al. The X chromosome and sex-specific effects in infectious disease susceptibility. Hum. Genomics 13, 2 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moore, J. T. et al. Disparities in incidence of COVID-19 among underrepresented racial/ethnic groups in counties identified as hotspots during June 5-18, 2020 – 22 states, February-June 2020. MMWR Morb. Mortal. Wkly Rep. 69, 1122–1126 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Figueroa, J. F. et al. Association of race, ethnicity, and community-level factors with COVID-19 cases and deaths across U.S. counties. Healthcare 9, 100495 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Jassat, W. et al. Corrigendum: The intersection of age, sex, race and socio-economic status in COVID-19 hospital admissions and deaths in South Africa. S. Afr. J. Sci. https://doi.org/10.17159/sajs.2022/13323C (2022).

  • Marshall, J. C. et al. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect. Dis. 20, e192–e197 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Docherty, A. B. et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO clinical characterisation protocol: prospective observational cohort study. BMJ 369, m1985 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Guan, W. et al. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 382, 1708–1720 (2020). This study evaluated confirmed cases of COVID-19 in over 550 hospitals in mainland China and was one of the first to characterize the range of symptomatology that occurs due to SARS-CoV-2 infection.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Williamson, E. J. et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 584, 430–436 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Centers for Disease Control and Prevention. Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19. CDC https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html (2020).

  • Kompaniyets, L. Underlying medical conditions and severe illness among 540,667 adults hospitalized with COVID-19, March 2020–March 2021. Prev. Chronic Dis. 18, E66 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mara, G., Nini, G. & Cotoraci, C. Impact of pulmonary comorbidities on COVID-19: acute and long-term evaluations. J. Clin. Med. 14, 1446 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jassat, W. et al. Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study. Lancet HIV 8, e554–e567 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vijenthira, A. et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood 136, 2881–2892 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fisher, A. M. et al. Outcomes of COVID-19 in hospitalized solid organ transplant recipients compared to a matched cohort of non-transplant patients at a national healthcare system in the United States. Clin. Transplant. 35, e14216 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Turtle, L. et al. Outcome of COVID-19 in hospitalised immunocompromised patients: an analysis of the WHO ISARIC CCP-UK prospective cohort study. PLoS Med. 20, e1004086 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Andersen, K. M. et al. Association between chronic use of immunosuppresive drugs and clinical outcomes from coronavirus disease 2019 (COVID-19) hospitalization: a retrospective cohort study in a large US health system. Clin. Infect. Dis. 73, e4124–e4130 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Barnett, K. et al. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet 380, 37–43 (2012).

    Article 
    PubMed 

    Google Scholar
     

  • Russell, C. D., Lone, N. I. & Baillie, J. K. Comorbidities, multimorbidity and COVID-19. Nat. Med. 29, 334–343 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chudasama, Y. V. et al. Patterns of multimorbidity and risk of severe SARS-CoV-2 infection: an observational study in the U.K. BMC Infect. Dis. 21, 908 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carmona-Pírez, J. et al. Identifying multimorbidity profiles associated with COVID-19 severity in chronic patients using network analysis in the PRECOVID Study. Sci. Rep. 12, 2831 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Delerue Matos, A., Fonseca de Paiva, A., Cunha, C. & Voss, G. Precautionary behaviours of individuals with multimorbidity during the COVID-19 pandemic. Eur. J. Ageing 19, 827–835 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Centers for Disease Control and Prevention. COVID Data Tracker 2023. CDC https://covid.cdc.gov/covid-data-tracker (2023).

  • Clark, E. C. et al. Changes to public health surveillance methods due to the COVID-19 pandemic: scoping review. JMIR Public Health Surveill. 10, e49185 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ibrahim, N. K. Epidemiologic surveillance for controlling Covid-19 pandemic: types, challenges and implications. J. Infect. Public Health 13, 1630–1638 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • World Health Organization. Statement on the Update of WHO’s Working Definitions and Tracking System for SARS-CoV-2 Variants of Concern and Variants of Interest. WHO https://www.who.int/news/item/16-03-2023-statement-on-the-update-of-who-s-working-definitions-and-tracking-system-for-sars-cov-2-variants-of-concern-and-variants-of-interest (2023).

  • World Health Organization. Updated Working Definitions and Primary Actions for SARS-CoV-2 Variants. WHO https://www.who.int/publications/m/item/updated-working-definitions-and-primary-actions-for–sars-cov-2-variants (2023).

  • Sanjuán, R., Nebot, M. R., Chirico, N., Mansky, L. M. & Belshaw, R. Viral mutation rates. J. Virol. 84, 9733–9748 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nobusawa, E. & Sato, K. Comparison of the mutation rates of human influenza A and B viruses. J. Virol. 80, 3675–3678 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Markov, P. V. et al. The evolution of SARS-CoV-2. Nat. Rev. Microbiol. 21, 361–379 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • DeGrace, M. M. et al. Defining the risk of SARS-CoV-2 variants on immune protection. Nature 605, 640–652 (2022). As novel SARS-CoV-2 variants emerged, the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme was established, which was a model of how to develop a coordinated approach to identify emerging variants, immune escape and protection, and predicted effects on vaccine protection.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davies, N. G. et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science 372, eabg3055 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tegally, H. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 592, 438–443 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Faria, N. R. et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science 372, 815–821 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Planas, D. et al. Reduced sensitivity of SARS-CoV-2 variant delta to antibody neutralization. Nature 596, 276–280 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rashedi, R. et al. Delta variant: the new challenge of COVID-19 pandemic, an overview of epidemiological, clinical, and immune characteristics. Acta Biomed. 93, e2022179 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Viana, R. et al. Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in Southern Africa. Nature 603, 679–686 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saito, A. et al. Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant. Cell Host Microbe 30, 1540–1555.e15 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gorbalenya, A. E. et al. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 5, 536–544 (2020).

    Article 

    Google Scholar
     

  • LaTourrette, K., Holste, N. M., Rodriguez-Peña, R., Leme, R. A. & Garcia-Ruiz, H. Genome-wide variation in Betacoronaviruses. J. Virol. 95, e00496 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou, H. et al. Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses. Cell 184, 4380–4391.e14 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wacharapluesadee, S. et al. Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia. Nat. Commun. 12, 972 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xiao, K. et al. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Nature 583, 286–289 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Stertz, S. et al. The intracellular sites of early replication and budding of SARS-coronavirus. Virology 361, 304–315 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • V’kovski, P., Kratzel, A., Steiner, S., Stalder, H. & Thiel, V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat. Rev. Microbiol. 19, 155–170 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Matsuyama, S. et al. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. J. Virol. 84, 12658–12664 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181, 271–280.e8 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Malone, B., Urakova, N., Snijder, E. J. & Campbell, E. A. Structures and functions of coronavirus replication–transcription complexes and their relevance for SARS-CoV-2 drug design. Nat. Rev. Mol. Cell Biol. 23, 21–39 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lan, J. et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 581, 215–220 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Letko, M., Marzi, A. & Munster, V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B Betacoronaviruses. Nat. Microbiol. 5, 562–569 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ziegler, C. G. K. et al. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell 181, 1016–1035.e19 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Beyerstedt, S., Casaro, E. B. & Rangel, É. B. COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. Eur. J. Clin. Microbiol. Infect. Dis. 40, 905–919 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Varga, Z. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 395, 1417–1418 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, H. et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet 395, 1517–1520 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, S. et al. SARS-CoV-2 Z-RNA activates the ZBP1-RIPK3 pathway to promote virus-induced inflammatory responses. Cell Res. 33, 201–214 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Van Cleemput, J. et al. Organ-specific genome diversity of replication-competent SARS-CoV-2. Nat. Commun. 12, 6612 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jacobs, J. L. et al. Plasma SARS-CoV-2 RNA levels as a biomarker of lower respiratory tract SARS-CoV-2 infection in critically ill patients with COVID-19. J. Infect. Dis. 226, 2089–2094 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hagman, K. et al. Prevalence and clinical relevance of viraemia in viral respiratory tract infections: a systematic review. Lancet Microbe 6, 100967 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Znaidia, M., Demeret, C., van der Werf, S. & Komarova, A. V. Characterization of SARS-CoV-2 evasion: interferon pathway and therapeutic options. Viruses 14, 1247 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Blanco-Melo, D. et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell 181, 1036–1045.e9 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hadjadj, J. et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Sci 369, 718–724 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Lee, J. S. et al. Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19. Sci. Immunol. 5, eabd1554 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou, Y. et al. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl Sci. Rev. 7, 998–1002 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zheng, M. et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell. Mol. Immunol. 17, 533–535 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schulte-Schrepping, J. et al. Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell 182, 1419–1440.e23 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sinha, P., Matthay, M. A. & Calfee, C. S. Is a ‘cytokine storm’ relevant to COVID-19? JAMA Intern. Med. 180, 1152–1154 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kox, M., Waalders, N. J. B., Kooistra, E. J., Gerretsen, J. & Pickkers, P. Cytokine levels in critically ill patients with COVID-19 and other conditions. JAMA 324, 1565–1567 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Del Valle, D. M. et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat. Med. 26, 1636–1643 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ramlall, V. et al. Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection. Nat. Med. 26, 1609–1615 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ackermann, M. et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid-19. N. Engl. J. Med. 383, 120–128 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pfeiler, S., Massberg, S. & Engelmann, B. Biological basis and pathological relevance of microvascular thrombosis. Thromb. Res. 133 (Suppl. 1), S35–S37 (2014).

    Article 
    PubMed 

    Google Scholar
     

  • Louis, T. J., Qasem, A., Abdelli, L. S. & Naser, S. A. Extra-pulmonary complications in SARS-CoV-2 infection: a comprehensive multi organ-system review. Microorganisms 10, 153 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Langford, B. J. et al. Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. Clin. Microbiol. Infect. 26, 1622–1629 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zuo, W. et al. The persistence of SARS-CoV-2 in tissues and its association with long COVID symptoms: a cross-sectional cohort study in China. Lancet Infect. Dis. 24, 845–855 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tomasicchio, M. et al. SARS-CoV-2 viral replication persists in the human lung for several weeks after symptom onset. Am. J. Respir. Crit. Care Med. 209, 840–851 (2004).

    Article 

    Google Scholar
     

  • Raglow, Z. et al. SARS-CoV-2 shedding and evolution in patients who were immunocompromised during the omicron period: a multicentre, prospective analysis. Lancet Microbe 5, e235–e246 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hettle, D., Hutchings, S., Muir, P. & Moran, E. Persistent SARS-CoV-2 infection in immunocompromised patients facilitates rapid viral evolution: retrospective cohort study and literature review. Clin. Infect. Pract. 16, 100210 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xu, J. et al. Chronic active SARS-CoV-2 in B-cell immunodeficiency. Innov. Med. 2, 100071 (2024).

    Article 
    CAS 

    Google Scholar
     

  • Ma, Q. et al. Global percentage of asymptomatic SARS-CoV-2 infections among the tested population and individuals with confirmed COVID-19 diagnosis: a systematic review and meta-analysis. JAMA Netw. Open 4, e2137257 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Struyf, T. et al. Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease. Cochrane Database Syst. Rev. 7, CD013665 (2020).

    PubMed 

    Google Scholar
     

  • Iuliano, A. D. Trends in disease severity and health care utilization during the early omicron variant period compared with previous SARS-CoV-2 high transmission periods — United States, December 2020–January 2022. MMWR Morb. Mortal. Wkly Rep. 71, 146–152 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Miller, J. M. et al. Guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2024 update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). Clin. Infect. Dis. https://doi.org/10.1093/cid/ciae104 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fragkou, P. C. et al. ESCMID COVID-19 guidelines: diagnostic testing for SARS-CoV-2. Clin. Microbiol. Infect. 28, 812–822 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Barak, N. et al. Lessons from applied large-scale pooling of 133,816 SARS-CoV-2 RT-PCR tests. Sci. Transl. Med. 13, eabf2823 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kidd, M. et al. S-variant SARS-CoV-2 lineage B1.1.7 is associated with significantly higher viral load in samples tested by taqpath polymerase chain reaction. J. Infect. Dis. 223, 1666–1670 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chu, V. T. et al. Comparison of home antigen testing with RT-PCR and viral culture during the course of SARS-CoV-2 infection. JAMA Intern. Med. 182, 701–709 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hirabayashi, E. et al. Comparison of diagnostic accuracy of rapid antigen tests for COVID-19 compared to the viral genetic test in adults: a systematic review and meta-analysis. JBI Evid. Synth. 22, 1939–2002 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hayden, M. K. et al. The Infectious Diseases Society of America guidelines on the diagnosis of COVID-19: antigen testing (January 2023). Clin. Infect. Dis. 78, e350–e384 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Soni, A. et al. Performance of rapid antigen tests to detect symptomatic and asymptomatic SARS-CoV-2 infection: a prospective cohort study. Ann. Intern. Med. 176, 975–982 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Frank, F. et al. Deep mutational scanning identifies SARS-CoV-2 nucleocapsid escape mutations of currently available rapid antigen tests. Cell 185, 3603–3616.e13 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Del Vecchio, C. et al. Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants. Nat. Commun. 13, 5870 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • To, K. K.-W. et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect. Dis. 20, 565–574 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yong, S. E. F. et al. Connecting clusters of COVID-19: an epidemiological and serological investigation. Lancet Infect. Dis. 20, 809–815 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, L.-L. et al. Contribution of low population immunity to the severe Omicron BA.2 outbreak in Hong Kong. Nat. Commun. 13, 3618 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, Y. et al. Longitudinal analysis of antibody dynamics in COVID-19 convalescents reveals neutralizing responses up to 16 months after infection. Nat. Microbiol. 7, 423–433 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Peto, L. et al. Diagnosis of SARS-CoV-2 infection with LamPORE, a high-throughput platform combining loop-mediated isothermal amplification and nanopore sequencing. J. Clin. Microbiol. 59, e03271-20 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lam, C. et al. SARS-CoV-2 genome sequencing methods differ in their abilities to detect variants from low-viral-load samples. J. Clin. Microbiol. 59, e0104621 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Miller, J. M. et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2018 update by the Infectious Diseases Society of America and the American Society for Microbiology. Clin. Infect. Dis. 67, e1 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Tsang, N. N. Y. et al. Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysis. Lancet Infect. Dis. 21, 1233–1245 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xie, J.-W. et al. Nasal swab is a good alternative sample for detecting SARS-CoV-2 with rapid antigen test: a meta-analysis. Travel Med. Infect. Dis. 52, 102548 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Waggoner, J. J. et al. Concordance of SARS-CoV-2 results in Self-collected nasal swabs vs swabs collected by health care workers in children and adolescents. JAMA 328, 935–940 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Baron, A. et al. Bronchoalveolar lavage in patients with COVID-19 with invasive mechanical ventilation for acute respiratory distress syndrome. Ann. Am. Thorac. Soc. 18, 723–726 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Laxton, C. S. et al. The potential of saliva as an accessible and sensitive sample type for the detection of respiratory pathogens and host immunity. Lancet Microbe 4, e837–e850 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Watkins, A. E. et al. Increased SARS-CoV-2 testing capacity with pooled saliva samples. Emerg. Infect. Dis. 27, 1184–1187 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Butler-Laporte, G. et al. Comparison of saliva and nasopharyngeal swab nucleic acid amplification testing for detection of SARS-CoV-2: a systematic review and meta-analysis. JAMA Intern. Med. 181, 353–360 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Centers for Disease Control and Prevention. Overview of Testing for SARS-CoV-2. CDC https://www.cdc.gov/covid/hcp/clinical-care/overview-testing-sars-cov-2.html (2025).

  • Total COVID-19 vaccine doses administered. Our World in Data https://ourworldindata.org/grapher/cumulative-covid-vaccinations?tab=table (2025).

  • Lives saved by COVID-19 vaccines. J. Paediatr. Child Health 222, 2129 (2022).

  • World Health Organization. WHO COVID-19 Dashboard. COVID-19 vaccination, world data. WHO https://data.who.int/dashboards/covid19/vaccines (2025).

  • BC Centre for Disease Control. World Health Organization (WHO) Emergency Use Authorization (EUA) Qualified COVID-19 Vaccines. WHO https://www.bccdc.ca/Health-Info-Site/Documents/COVID-19_vaccine/WHO-EUA-qualified-covid-vaccines.pdf (2024).

  • World Health Organization. WHO Roadmap on Uses of COVID-19 Vaccines in the Context of Omicron and High Population Immunity. WHO https://www.who.int/publications/i/item/WHO-2019-nCoV-Vaccines-SAGE-Prioritization-2023.2 (2023).

  • Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2021). The pivotal phase III study demonstrated that the mRNA-1273 vaccine provided 94.1% efficacy against COVID-19 illness and provided essential data to proceed to Emergency Use Authorization and licensure.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Falsey, A. R. et al. Phase 3 safety and efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 vaccine. N. Engl. J. Med. 385, 2348–2360 (2021). The phase III study demonstrated that the AZD1222 vaccine had an overall vaccine efficacy of 74% and a vaccine efficacy of 83.5% in adults >65 years of age.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020). This pivotal phase III study demonstrated that the BNT162b2 vaccine provided 95% efficacy against COVID-19 in persons aged ≥16 years and provided essential data to proceed to Emergency Use Authorization and licensure.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Heath, P. T. et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N. Engl. J. Med. 385, 1172–1183 (2021). This phase III study demonstrated that the recombinant nanoparticle vaccine NVX-CoV2373 provided 89.7% efficacy against COVID-19 in adults 18–84 years of age.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sadoff, J. et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N. Engl. J. Med. 384, 2187–2201 (2021). This phase III study demonstrated that a single dose of the recombinant human adenovirus vector type 26 SARS-CoV-2 vaccine provided 66.9% efficacy against COVID-19 in adults ≥18 years of age.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dayan, G. H. et al. Efficacy of a bivalent (D614+B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial. Lancet Respir. Med. 11, 975–990 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gilbert, P. B. et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science 375, 43–50 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Branche, A. R. et al. Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial. Nat. Med. 29, 2334–2346 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • US Food and Drug Administration. Novavax COVID-19 vaccine, adjuvanted. FDA https://www.fda.gov/vaccines-blood-biologics/coronavirus-covid-19-cber-regulated-biologics/novavax-covid-19-vaccine-adjuvanted (2025).

  • US Food and Drug Administration. FDA Approves and Authorizes Updated mRNA COVID-19 Vaccines to Better Protect Against Currently Circulating Variants. FDA https://www.fda.gov/news-events/press-announcements/fda-approves-and-authorizes-updated-mrna-covid-19-vaccines-better-protect-against-currently (2024).

  • Menegale, F. et al. Evaluation of waning of SARS-CoV-2 vaccine–induced immunity: a systematic review and meta-analysis. JAMA Netw. Open 6, e2310650 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nordström, P., Ballin, M. & Nordström, A. Risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals with natural and hybrid immunity: a retrospective, total population cohort study in Sweden. Lancet Infect. Dis. 22, 781–790 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arbel, R. et al. Effectiveness of a bivalent mRNA vaccine booster dose to prevent severe COVID-19 outcomes: a retrospective cohort study. Lancet Infect. Dis. 23, 914–921 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Centers for Disease Control and Prevention. Vaccines for Moderately to Severely Immunocompromised People. CDC https://www.cdc.gov/covid/vaccines/immunocompromised-people.html (2025).

  • Mayr, F. B., Talisa, V. B., Shaikh, O., Yende, S. & Butt, A. A. Effectiveness of homologous or heterologous Covid-19 boosters in veterans. N. Engl. J. Med. 386, 1375–1377 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Atmar, R. L. et al. Homologous and heterologous Covid-19 booster vaccinations. N. Engl. J. Med. 386, 1046–1057 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lazarus, R. et al. Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial. Lancet 398, 2277 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Debes, A. K. et al. Association of vaccine type and prior SARS-CoV-2 Infection with symptoms and antibody measurements following vaccination among health care workers. JAMA Intern. Med. 181, 1660–1662 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Karlstad, Ø. et al. SARS-CoV-2 vaccination and myocarditis in a nordic cohort study of 23 million residents. JAMA Cardiol. 7, 600–612 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Buchan, S. A. et al. Epidemiology of myocarditis and pericarditis following mRNA vaccination by vaccine product, schedule, and interdose interval among adolescents and adults in Ontario, Canada. JAMA Netw. Open 5, e2218505 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Su, J. R. Myopericarditis following COVID-19 vaccination : updates from the Vaccine Adverse Event Reporting System (VAERS). CDC https://stacks.cdc.gov/view/cdc/109492 (2021).

  • Jeong, Y. D. et al. Global burden of vaccine-associated Guillain-Barré syndrome over 170 countries from 1967 to 2023. Sci. Rep. 14, 24561 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Obeid, M. et al. Humoral responses against variants of concern by COVID-19 mRNA vaccines in immunocompromised patients. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2022.0446 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sherman, A. C. et al. Severe acute respiratory syndrome coronavirus 2 messenger RNA vaccines in allogeneic hematopoietic stem cell transplant recipients: immunogenicity and reactogenicity. Clin. Infect. Dis. 75, e920–e923 (2021).

    Article 

    Google Scholar
     

  • Ghione, P. et al. Impaired humoral responses to COVID-19 vaccination in patients with lymphoma receiving B-cell–directed therapies. Blood 138, 811–814 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cowan, J., Amson, A., Christofides, A. & Chagla, Z. Monoclonal antibodies as COVID-19 prophylaxis therapy in immunocompromised patient populations. Int. J. Infect. Dis. 134, 228–238 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Iketani, S. et al. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature 604, 553–556 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Choudhary, M. C. et al. Emergence of SARS-CoV-2 escape mutations during bamlanivimab therapy in a phase II randomized clinical trial. Nat. Microbiol. 7, 1906–1917 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schmidt, P., Li, Y. & Popejoy, M. Immunobridging for pemivibart, a monoclonal antibody for prevention of Covid-19. N. Engl. J. Med. 391, 1860–1862 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lam, C. & Patel, P. Nirmatrelvir-Ritonavir. StatPearls [Internet] https://www.ncbi.nlm.nih.gov/books/NBK585126/ (updated 8 August 2023).

  • Hammond, J. et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N. Engl. J. Med. 386, 1397–1408 (2022). A phase II–III double-blind, randomized, controlled trial in unvaccinated, non-hospitalized adults at high risk for progression to severe COVID-19, that showed a significant decrease in risk of progression to severe COVID-19 in the nirmatrelvir-ritonavir group.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hammond, J. et al. Nirmatrelvir for vaccinated or unvaccinated adult outpatients with Covid-19. N. Engl. J. Med. 390, 1186–1195 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jayk Bernal, A. et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N. Engl. J. Med. 386, 509–520 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Butler, C. C. et al. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet 401, 281–293 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • National Institute for Health and Care Excellence. Evidence Review for Molnupiravir: NICE COVID-19 Rapid Guideline: Managing COVID-19: Evidence Review Q (NICE, 2022).

  • Gupta, A. et al. Effect of sotrovimab on hospitalization or death among high-risk patients with mild to moderate COVID-19: a randomized clinical trial. JAMA 327, 1236–1246 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Focosi, D., Casadevall, A., Franchini, M. & Maggi, F. Sotrovimab: a review of its efficacy against SARS-CoV-2 variants. Viruses 16, 217 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Montgomery, H. et al. Efficacy and safety of intramuscular administration of tixagevimab-cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Respir. Med. 10, 985–996 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ragonnet-Cronin, M. et al. Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy. Nat. Commun. 14, 3334 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nielsen, F. M. et al. Lower vs higher oxygenation target and days alive without life support in COVID-19: the HOT-COVID randomized clinical trial. JAMA 331, 1185–1194 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cajanding, R. Oxygen use and saturation targets in patients with COVID-19: Are we giving too much or aiming too low? Nurs. Crit. Care 27, 282–285 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Beigel, J. H. et al. Remdesivir for the treatment of Covid-19 — final report. N. Engl. J. Med. 383, 1813–1826 (2020). The double-blind, randomized, placebo-controlled trial of intravenous remdesivir as compared with placebo in hospitalized adults with COVID-19, demonstrating that remdesivir was superior to placebo in shortening the time to recovery from infection.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pan, H. et al. Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. Lancet 399, 1941–1953 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Amstutz, A. et al. Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials. Lancet Respir. Med. 11, 453–464 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mozaffari, E. et al. Remdesivir is associated with reduced mortality in COVID-19 patients requiring supplemental oxygen including invasive mechanical ventilation across SARS-CoV-2 variants. Open Forum Infect. Dis. 10, ofad482 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Paules, C. I. et al. A risk profile using simple hematologic parameters to assess benefits from baricitinib in patients hospitalized with COVID-19: a post hoc analysis of the adaptive COVID-19 treatment trial-2. Ann. Intern. Med. 177, 343–352 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Singh, K. et al. SARS-CoV-2 RNA and nucleocapsid antigen are blood biomarkers associated with severe disease outcomes that improve in response to remdesivir. J. Infect. Dis. 230, 624–634 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gottlieb, R. L. et al. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N. Engl. J. Med. 386, 305–315 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • RECOVERY Collaborative Group et al. Dexamethasone in hospitalized patients with Covid-19. N. Engl. J. Med. 384, 693–704 (2021).

    Article 

    Google Scholar
     

  • Covello, R. D. et al. Meta-analysis of glucocorticoids for Covid-19 patients not receiving oxygen. NEJM Evid. 2, EVIDoa2200283 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Angus, D. C. et al. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA 324, 1317–1329 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sterne, J. A. C. et al. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association between systemic corticosteroids and mortality among critically ill patients with COVID-19. JAMA 324, 1330–1341 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • The REMAP-CAP Investigators. Interleukin-6 receptor antagonists in critically Ill patients with Covid-19. N. Engl. J. Med. 384, 1491–1502 (2021).

    Article 

    Google Scholar
     

  • Godolphin, P. J. et al. Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: a network meta-analysis. PLoS ONE 17, e0270668 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rosas, I. O. et al. Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial. Intensive Care Med. 47, 1258–1270 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • MArconi, V. C. et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir. Med. 9, 1407–1418 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ely, E. W. et al. Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial. Lancet Respir. Med. 10, 327–336 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kalil, A. C. et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N. Engl. J. Med. 384, 795–807 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • RECOVERY Collaborative Group. Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis. Lancet 400, 359–368 (2022).

    Article 

    Google Scholar
     

  • Amstutz, A. et al. Effects of Janus kinase inhibitors in adults admitted to hospital due to COVID-19: a systematic review and individual participant data meta-analysis of randomised clinical trials. Lancet Respir. Med. 13, 530–544 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • RECOVERY Collaborative Group. Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 399, 665–676 (2022).

    Article 

    Google Scholar
     

  • The ATTACC, ACTIV-4a, and REMAP-CAP Investigators. Therapeutic anticoagulation with heparin in noncritically Ill patients with Covid-19. N. Engl. J. Med. 385, 790–802 (2021).

    Article 

    Google Scholar
     

  • Stone, G. W. et al. Randomized trial of anticoagulation strategies for noncritically Ill patients hospitalized with COVID-19. JACC 81, 1747–1762 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lopes, R. D. et al. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet 397, 2253–2263 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bradbury, C. A., Lawler, P. R., McVerry, B. J., Zarychanski, R. & REMAP-C. A. P. Investigators. Continuation of therapeutic dose heparin for critically ill patients with COVID-19. Intensive Care Med. 49, 873–875 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Goligher, E. C. et al. Heterogeneous treatment effects of therapeutic-dose heparin in patients hospitalized for COVID-19. JAMA 329, 1066–1077 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • RECOVERY Collaborative Group. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 399, 143–151 (2022).

    Article 

    Google Scholar
     

  • REMAP-CAP Writing Committee for the REMAP-CAP Investigators. Effect of antiplatelet therapy on survival and organ support in critically Ill patients with COVID-19. JAMA 327, 1247–1259 (2022).

    Article 
    PubMed Central 

    Google Scholar
     

  • Berger, J. S. et al. Effect of P2Y12 inhibitors on survival free of organ support among hospitalized patients with COVID-19. JAMA Netw. Open 6, e2314428 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Writing Committee for the REMAP-CAP Investigators. Long-term (180-day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP randomized clinical trial. JAMA 329, 39–51 (2023).

    Article 

    Google Scholar
     

  • Calfee, C. S. et al. Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial. Lancet Respir. Med. 6, 691–698 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lao, U.-S., Law, C.-F., Baptista-Hon, D. T. & Tomlinson, B. Systematic review and meta-analysis of statin use and mortality, intensive care unit admission and requirement for mechanical ventilation in COVID-19 patients. J. Clin. Med. 11, 5454 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • The REMAP-CAP Investigators. Simvastatin in critically Ill patients with Covid-19. N. Engl. J. Med. 389, 2341–2354 (2023).

    Article 

    Google Scholar
     

  • Evans, R. A. et al. Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study. Lancet Reg. Health Eur. 35, 100747 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Little, J. S. et al. Protracted SARS-CoV-2 infection in B-cell depleted patients: immunologic andiral characteristics and response to dual and extended antiviral therapy. Clin. Infect. Dis. https://doi.org/10.1093/cid/ciaf383 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Weinstein, E. et al. Extended nirmatrelvir–ritonavir treatment durations for immunocompromised patients with COVID-19 (EPIC-IC): a placebo-controlled, randomised, double-blind, phase 2 trial. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(25)00221-X (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Axfors, C. et al. Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials. BMC Infect. Dis. 21, 1170 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • RECOVERY Collaborative Group. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet 397, 2049–2059 (2021).

    Article 

    Google Scholar
     

  • Writing Committee for the REMAP-CAP Investigators. Effect of convalescent plasma on organ support–free days in critically Ill patients with COVID-19 a randomized clinical trial. JAMA 326, 1690–1702 (2021).

    Article 
    PubMed Central 

    Google Scholar
     

  • Misset, B. et al. Convalescent plasma for Covid-19–induced ARDS in mechanically ventilated patients. N. Engl. J. Med. 389, 1590–1600 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Senefeld, J. W. et al. COVID-19 convalescent plasma for the treatment of immunocompromised patients. JAMA Netw. Open 6, e2250647 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huygens, S. et al. Clinical and virological outcome of monoclonal antibody therapies across SARS-CoV-2 variants in 245 immunocompromised patients: a multicenter prospective cohort study. Clin. Infect. Dis. 78, 1514–1521 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Allotey, J. et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ 370, m3320 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Chourasia, P. et al. Paxlovid (Nirmatrelvir and Ritonavir) use in pregnant and lactating woman: current evidence and practice guidelines — a scoping review. Vaccines 11, 107 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Uktis. Medications Used to Treat Covid 19 in Pregnancy. Uktis https://uktis.org/monographs/medications-used-to-treat-covid-19-in-pregnancy/ (2025).

  • Jorgensen, S. C. J. & Lapinsky, S. E. Tocilizumab for coronavirus disease 2019 in pregnancy and lactation: a narrative review. Clin. Microbiol. Infect. 28, 51–57 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nana, M. et al. Use of interleukin-6 receptor antibodies in the second and third trimester of pregnancy: a retrospective cohort study. Lancet Rheumatol. 6, e625–e635 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ferreira, L. N., Pereira, L. N., da Fé Brás, M. & Ilchuk, K. Quality of life under the COVID-19 quarantine. Qual. Life Res. 30, 1389–1405 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chu, I. Y.-H., Alam, P., Larson, H. J. & Lin, L. Social consequences of mass quarantine during epidemics: a systematic review with implications for the COVID-19 response. J. Travel. Med. 27, taaa192 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Long, D. et al. Health-related quality of life and mental well-being of healthy and diseased persons in 8 countries: does stringency of government response against early COVID-19 matter? SSM Popul. Health 15, 100913 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yin, S., Njai, R., Barker, L., Siegel, P. Z. & Liao, Y. Summarizing health-related quality of life (HRQOL): development and testing of a one-factor model. Popul. Health Metr. 14, 22 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • EQ-5D-5L – EQ-5D. EUROQOL https://euroqol.org/register/obtain-eq-5d/available-versions/ (2025).

  • Ware, J. E. & Sherbourne, C. D. The MOS 36-item short-form health survey (SF-36). I. conceptual framework and item selection. Med. Care 30, 473–483 (1992).

    Article 
    PubMed 

    Google Scholar
     

  • Nandasena, H. M. R. K. G., Pathirathna, M. L., Atapattu, A. M. M. P. & Prasanga, P. T. S. Quality of life of COVID 19 patients after discharge: systematic review. PLoS ONE 17, e0263941 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Poudel, A. N. et al. Impact of Covid-19 on health-related quality of life of patients: a structured review. PLoS ONE 16, e0259164 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • van der Molen, T. et al. Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual. Life Outcomes 1, 13 (2003).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jones, P. W., Quirk, F. H. & Baveystock, C. M. The St George’s Respiratory Questionnaire. Respir. Med. 85, 25–31 (1991).

    Article 
    PubMed 

    Google Scholar
     

  • Herdman, M. et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual. Life Res. 20, 1727–1736 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hay, J. W. et al. A US population health survey on the impact of COVID-19 using the EQ-5D-5L. J. Gen. Intern. Med. 36, 1292–1301 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lubetkin, E. I., Long, D., Haagsma, J. A., Janssen, M. F. & Bonsel, G. J. Health inequities as measured by the EQ-5D-5L during COVID-19: results from New York in healthy and diseased persons. PLoS ONE 17, e0272252 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ping, W. et al. Evaluation of health-related quality of life using EQ-5D in China during the COVID-19 pandemic. PLoS ONE 15, e0234850 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Barani, S. et al. Health-related quality of life among COVID-19 individuals: a cross-sectional study in Tamil Nadu, India. Clin. Epidemiol. Glob. Health 13, 100943 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Violato, M. et al. The COVID-19 pandemic and health-related quality of life across 13 high- and low-middle-income countries: a cross-sectional analysis. PLoS Med. 20, e1004146 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Aburto, J. M. et al. Quantifying impacts of the COVID-19 pandemic through life-expectancy losses: a population-level study of 29 countries. Int. J. Epidemiol. 51, 63–74 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Heuveline, P. & Tzen, M. Beyond deaths per capita: comparative COVID-19 mortality indicators. BMJ Open 11, e042934 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Andrasfay, T. & Goldman, N. Reductions in US life expectancy during the COVID-19 pandemic by race and ethnicity: is 2021 a repetition of 2020? PLoS ONE 17, e0272973 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Andrasfay, T. & Goldman, N. Association of the COVID-19 pandemic with estimated life expectancy by race/ethnicity in the United States, 2020. JAMA Netw. Open 4, e2114520 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Woolf, S. H., Masters, R. K. & Aron, L. Y. Effect of the covid-19 pandemic in 2020 on life expectancy across populations in the USA and other high income countries: simulations of provisional mortality data. BMJ 373, n1343 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Huang, G. et al. The effect of the COVID-19 pandemic on life expectancy in 27 countries. Sci. Rep. 13, 8911 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • United Nations. World Population Prospects 2019: Highlights. United Nations https://population.un.org/wpp/ (2024).

  • Islam, N. et al. Effects of covid-19 pandemic on life expectancy and premature mortality in 2020: time series analysis in 37 countries. BMJ 375, e066768 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Lytras, S., Xia, W., Hughes, J., Jiang, X. & Robertson, D. L. The animal origin of SARS-CoV-2. Science 373, 968–970 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ellwanger, J. H. & Chies, J. A. B. Zoonotic spillover: understanding basic aspects for better prevention. Genet. Mol. Biol. 44, e20200355 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kessler, S., Harder, T. C., Schwemmle, M. & Ciminski, K. Influenza a viruses and zoonotic events — are we creating our own reservoirs? Viruses 13, 2250 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kawasaki, J., Suzuki, T. & Hamada, M. Hidden challenges in evaluating spillover risk of zoonotic viruses using machine learning models. Commun. Med. 5, 187 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xiao, X., Newman, C., Buesching, C. D., Macdonald, D. W. & Zhou, Z.-M. Animal sales from Wuhan wet markets immediately prior to the COVID-19 pandemic. Sci. Rep. 11, 11898 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • World Health Organization. One Health. WHO https://www.who.int/health-topics/one-health (2025).

  • Centers for Disease Control and Prevention (CDC). Update: outbreak of severe acute respiratory syndrome — worldwide, 2003. MMWR Morb. Mortal. Wkly. Rep. 52, 241–246, 248 (2003).


    Google Scholar
     

  • Olsen, S. J. et al. Transmission of the severe acute respiratory syndrome on aircraft. N. Engl. J. Med. 349, 2416–2422 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fang, Y., Nie, Y. & Penny, M. Transmission dynamics of the COVID-19 outbreak and effectiveness of government interventions: a data-driven analysis. J. Med. Virol. 92, 645 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kucharski, A. J. et al. Early dynamics of transmission and control of COVID-19: a mathematical modelling study. Lancet Infect. Dis. 20, 553 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Akhmetzhanov, A. R. et al. Transmission dynamics and effectiveness of control measures during COVID-19 surge, Taiwan, April–August 2021. Emerg. Infect. Dis. 28, 2051–2059 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chernozhukov, V., Kasahara, H. & Schrimpf, P. The association of opening K-12 schools with the spread of COVID-19 in the United States: county-level panel data analysis. Proc. Natl Acad. Sci. USA 118, e2103420118 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cevik, M., Kuppalli, K., Kindrachuk, J. & Peiris, M. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ 371, m3862 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Gilbert, P. B. et al. A Covid-19 milestone attained — a correlate of protection for vaccines. N. Engl. J. Med. 387, 2203–2206 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Sherman, A. C., Desjardins, M. & Baden, L. R. Vaccine-induced severe acute respiratory syndrome coronavirus 2 antibody response and the path to accelerating development (Determining a Correlate of Protection). Clin. Lab. Med. 42, 111–128 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Goldblatt, D., Alter, G., Crotty, S. & Plotkin, S. A. Correlates of protection against SARS-CoV-2 infection and COVID-19 disease. Immunol. Rev. https://doi.org/10.1111/imr.13091 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davis, H. E., McCorkell, L., Vogel, J. M. & Topol, E. J. Long COVID: major findings, mechanisms and recommendations. Nat. Rev. Microbiol. 21, 133–146 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Project NextGen: Next Generation Medical Countermeasures. US Department of Health and Human Services https://medicalcountermeasures.gov/nextgen (2025).

  • Bussink-Voorend, D., Hautvast, J. L. A., Vandeberg, L., Visser, O. & Hulscher, M. E. J. L. A systematic literature review to clarify the concept of vaccine hesitancy. Nat. Hum. Behav. 6, 1634–1648 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Cascini, F., Pantovic, A., Al-Ajlouni, Y., Failla, G. & Ricciardi, W. Attitudes, acceptance and hesitancy among the general population worldwide to receive the COVID-19 vaccines and their contributing factors: a systematic review. EClinicalMedicine 40, 101113 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chan, L. et al. Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection. Sci. Transl. Med. 17, eadq1086 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cao, B. et al. Oral simnotrelvir for adult patients with mild-to-moderate Covid-19. N. Engl. J. Med. 390, 230–241 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fan, X. et al. Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study. Lancet Infect. Dis. 24, 129–139 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Zhan, Y. et al. Leritrelvir for the treatment of mild or moderate COVID-19 without co-administered ritonavir: a multicentre randomised, double-blind, placebo-controlled phase 3 trial. eClinicalMedicine 67, 102359 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Yotsuyanagi, H. et al. Efficacy and safety of 5-Day oral ensitrelvir for patients with mild to moderate COVID-19: the SCORPIO-SR randomized clinical trial. JAMA Netw. Open 7, e2354991 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lu, H. et al. Efficacy and safety of GST-HG171 in adult patients with mild to moderate COVID-19: a randomised, double-blind, placebo-controlled phase 2/3 trial. eClinicalMedicine 71, 102582 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • World Health Organization. Coronavirus Disease (COVID-19). Strategy and Planning. WHO https://www.who.int/emergencies/diseases/novel-coronavirus-2019/strategies-and-plans (2023).

  • Source link

    Get RawNews Daily

    Stay informed with our RawNews daily newsletter email

    Injury Notes: Crawford, Kerkering, Murphy, Hernández

    KitKat theft: 12 tons of chocolate bars stolen during Europe transport

    Martin Short Spotted Out For First Time Since Daughter Katherine’s Death

    Multiple Indycar Drivers Crash During Practice for Grand Prix in Alabama