covid-19
Ongoing updates of key clinical trial advances and new study data for common conditions.

By Lisa Kuhns, PhD

Published October 28, 2024

Introduction

COVID-19, caused by the SARS-CoV-2 virus, remains a highly transmissible and widespread disease, affecting individuals globally since its emergence in December 2019.1 The disease primarily impacts the respiratory system but can cause symptoms affecting multiple organs, ranging from mild to severe.1 As of June 2024, nearly 1.2 million deaths have been reported in the United States, with over 6.9 million deaths globally.1,2 Vaccination campaigns have resulted in the administration of more than 13 billion doses worldwide, significantly reducing severe illness and deaths. However, COVID-19 continues to pose risks, particularly for older adults, immunocompromised individuals, and those with underlying health conditions.2

Recent data from October 2024 show early indicators of ongoing transmission. Test positivity rates in the United States were 6.3% in the week ending October 12, 2024, slightly lower than the previous week’s 7.6%.3 Emergency department visits for COVID-19 accounted for 0.7% of cases in the same week, down from 0.8%.3 Hospitalizations stood at a rate of 3.2 per 100,000 people, with a slight decrease from 3.7 the previous week.3 Meanwhile, COVID-19-related deaths comprised 1.5% of all U.S. deaths, down from 1.8% in the previous week.3 These statistics highlight the continued impact of the virus and the importance of monitoring its progression as new variants emerge. Public health efforts remain crucial in reducing transmission and protecting vulnerable populations.

Etiology

COVID-19 is caused by the SARS-CoV-2 virus, which primarily spreads through respiratory droplets and aerosols emitted when an infected person coughs, sneezes, talks, or even breathes.4 This mode of transmission can occur even from individuals who do not exhibit symptoms, making it particularly challenging to control. The virus can be inhaled by people nearby or can land on surfaces, where it may be transferred to others who touch these surfaces and then their faces.4 While surface transmission is less common, it remains a possible route of infection.4 The virus' ability to mutate also plays a role in its spread and persistence, as these changes can sometimes reduce the effectiveness of immunity gained from previous infections or vaccinations, leading to potential reinfections.1 Moreover, SARS-CoV-2 can infect some animals like cats and dogs, although human-to-animal transmission is rare.4

The risk of contracting COVID-19 increases with certain factors such as close contact with an infected person, especially in poorly ventilated spaces or crowded settings.4 Spending extended periods in close proximity to someone with COVID-19 significantly raises the likelihood of transmission. Although anyone can contract the virus, certain groups are at higher risk for severe illness.4 These include older adults, individuals with underlying health conditions such as heart disease, diabetes, or obesity, and those who are unvaccinated. Additionally, people with compromised immune systems or other medical conditions like cancer or dementia face increased risks.4 Understanding these transmission routes and risk factors is crucial for implementing effective preventive measures such as vaccination, mask-wearing, and maintaining good ventilation in indoor spaces to mitigate the spread of COVID-19.

Screening and Diagnosis

COVID-19 screening and diagnosis primarily involve two types of tests: diagnostic tests, which detect current infections, and antibody tests, which identify past infections.5 Diagnostic tests are further divided into molecular tests (such as polymerase chain reaction [PCR] tests) and antigen tests (often called rapid or at-home tests). Molecular tests are highly accurate but may take days to process, while antigen tests provide quick results but are less sensitive, especially for asymptomatic cases. Testing is recommended for individuals with symptoms, those exposed to COVID-19, before contact with high-risk individuals, or as advised by healthcare providers.4

Multiple options exist for getting tested, including at-home tests, community testing sites, and health care providers. When interpreting results, a positive test on either type of diagnostic test likely indicates a current infection. For antigen tests, the FDA recommends repeat testing to confirm negative results, especially for symptomatic individuals.5  It's important to note that even with a negative result, continuing precautionary measures is crucial to prevent the spread of COVID-19.5

COVID-19 diagnostic tests use nose, throat, or saliva samples to detect viral material. Molecular tests, like PCR and other nucleic acid amplification tests (NAATs), look for the virus’ genetic material and are highly sensitive, making them a reliable option for diagnosing an infection.5  On the other hand, antigen tests, often called rapid tests, detect specific proteins from the virus and can be performed at home or in clinical settings, delivering faster results but with less accuracy than molecular tests. Antigen tests are more effective when symptoms are present, and it is recommended to retest within 48 hours if a negative result is obtained.5

The Infectious Diseases Society of America (IDSA) guidelines recommend using a SARS-CoV-2 NAAT for symptomatic individuals suspected of having COVID-19, with swab specimens collected from various sites such as the nasopharynx or saliva.6 Rapid or standard laboratory-based NAATs are suggested, but routine repeat testing is not recommended for those with an initial negative result. For asymptomatic individuals with known exposure, testing is advised, especially if they have clinical or epidemiologic reasons. However, routine testing is not suggested for asymptomatic individuals without known exposure who are hospitalized or undergoing procedures.6 The guidelines also advise against routinely repeating NAAT before procedures in patients with a recent COVID-19 history and suggest against using NAAT to guide release from isolation. Home testing is neither recommended nor discouraged due to insufficient evidence.6

The IDSA guidelines recommend against using serologic testing to diagnose SARS-CoV-2 infection within the first 2 weeks of symptom onset due to low accuracy, especially in vaccinated individuals or those with prior infections.7 They advise against using IgG antibodies for diagnosing COVID-19 in symptomatic patients with high suspicion and negative NAAT results. For diagnosing multisystem inflammatory syndrome in children (MIS-C), combining IgG antibody testing with NAAT is recommended.7 When confirming past infection, testing for IgG, IgG/IgM, or total antibodies three to five weeks after symptoms is suggested, avoiding IgM tests. Assays targeting nucleocapsid protein are preferred over spike protein due to vaccination effects. Routine serologic testing is not recommended for individuals with previous infection or vaccination, as it does not improve patient outcomes.7

The IDSA provides several recommendations for antigen (Ag) testing in COVID-19.8 For symptomatic individuals, a single Ag test is recommended over no test, but standard NAAT (e.g., RT-PCR) is preferred when available. If NAAT results are delayed, rapid Ag testing is suggested. For asymptomatic individuals with known exposure, a single Ag test is suggested in specific situations, though standard NAAT is preferred when available.8 If the first Ag test is negative, repeat testing is recommended. The panel suggests either point-of-care or laboratory-based Ag testing and supports both observed and unobserved self-collection of swab specimens. However, the panel does not make specific recommendations for testing in educational or workplace settings, or before large gatherings, due to insufficient evidence.8

Treatment and Management

COVID-19 treatment approaches emphasize a tailored use of antivirals, anti-inflammatory agents, and immunomodulators across different stages of infection.9 Early-phase infection, marked by high viral load before a significant immune response, is targeted with antiviral therapies to curb viral replication. Approved under the FDA's Emergency Use Authorization (EUA), the oral antivirals nirmatrelvir/ritonavir and molnupiravir, alongside the intravenous remdesivir, are primary options for high-risk patients with mild to moderate symptoms.These antivirals are most effective when administered within 5-7 days of symptom onset, with rapid initiation critical to preventing severe disease progression. However, as circulating variants evolve, especially within the Omicron lineage, the efficacy of certain antibody treatments has declined, rendering them ineffective in the United States as of early 2023.9

Monoclonal antibodies and convalescent plasma, which provide passive immunity by directly targeting SARS-CoV-2, have become less viable due to variant resistance.9 For instance, FDA emergency authorization for monoclonal antibodies like bamlanivimab, casirivimab/imdevimab, and bebtelovimab has been rescinded due to their reduced effectiveness against current strains. High-titer convalescent plasma remains an option for immunocompromised patients at high risk, though it is no longer advised for broader use, given the limited demonstrated benefit.9

In patients with severe COVID-19, particularly those requiring oxygen support due to hypoxia, anti-inflammatory drugs become central to treatment, addressing the excessive immune response responsible for much of the disease’s severe pathology.Corticosteroids, especially dexamethasone, are widely endorsed and have shown mortality benefits in both severe and critical COVID-19 cases. Other corticosteroids, such as hydrocortisone or methylprednisolone, serve as alternatives, especially in the absence of dexamethasone, with evidence supporting their role in reducing immune-mediated lung damage.9 For patients whose inflammatory response escalates despite corticosteroids, IL-6 inhibitors (tocilizumab and sarilumab) and Janus kinase (JAK) inhibitors (baricitinib and tofacitinib) offer additional support. Tocilizumab and baricitinib are preferred, particularly in patients with elevated markers like C-reactive protein (CRP), as studies indicate they can reduce the risk of clinical deterioration.9

For patients in critical condition requiring high-flow oxygen or non-invasive ventilation, these anti-inflammatory agents remain key, while remdesivir is generally not recommended due to a lack of observed benefit in this population.In critically ill patients needing mechanical ventilation or extracorporeal membrane oxygenation (ECMO), corticosteroids remain the cornerstone of therapy. However, additional treatments with IL-6 inhibitors or JAK inhibitors are considered based on patient inflammation levels, though evidence supporting their use in these patients is less robust.9 For example, baricitinib has shown some benefit in reducing mortality among ventilated patients and may be used as an alternative when IL-6 inhibitors are unavailable.9

In mild to moderate COVID-19 cases, IDSA advises against treatments like hydroxychloroquine, azithromycin, and ivermectin, based on evidence indicating limited efficacy and potential risks. Similarly, systemic corticosteroids are discouraged in non-hypoxic patients, as studies suggest they may increase mortality risks in mild cases.9 The IDSA also suggests fluvoxamine only within clinical trials, as further research is needed to establish any conclusive benefit. Other agents such as famotidine, colchicine, and anakinra are also not recommended due to low-certainty evidence for their benefit.9

Janus kinase (JAK) inhibitors, particularly baricitinib, have garnered attention for their role in mitigating severe COVID-19 symptoms by targeting cytokine-driven inflammation.9 Baricitinib, approved in conjunction with corticosteroids, shows potential in reducing the need for mechanical ventilation in high-risk patients. For those intolerant to corticosteroids, baricitinib with remdesivir offers an alternative approach. Tofacitinib, another JAK inhibitor, is also advised for severe cases but should not be combined with IL-6 inhibitors, given potential safety concerns.9

Multidisciplinary Approach

Multidisciplinary care has emerged as a crucial approach in managing patients with COVID-19, given the complex and multifaceted nature of the disease.10,11 This approach brings together health care professionals from various specialties to provide comprehensive care that addresses the wide range of symptoms and complications associated with COVID-19. The team typically includes infectious disease specialists, pulmonologists, cardiologists, neurologists, physical and occupational therapists, psychologists, dietitians, nurses, and social workers.11,12

The multidisciplinary care model for those with COVID-19 encompasses several key aspects.10,12 Given the virus' primary impact on the lungs, respiratory support and management are often at the forefront. Cardiovascular care is also critical, as the disease can significantly affect heart function. Neurological assessment and treatment are necessary to address the various neurological symptoms that some patients experience. Physical rehabilitation plays a vital role in helping patients regain strength and function, particularly after prolonged hospitalization or intensive care. Psychological support is essential in managing the mental health impacts of the disease and prolonged isolation. Nutritional guidance helps in maintaining overall health and supporting recovery.10,12

As the pandemic has progressed, many hospitals have established dedicated post-COVID or "long COVID" clinics. These clinics feature multidisciplinary teams that focus on addressing the long-term effects of the disease, which can persist for months after the initial infection.10,13 This comprehensive follow-up care is crucial in supporting patients' full recovery and addressing any lingering symptoms or complications.

The COVID-19 pandemic has posed significant challenges to delivering multidisciplinary care, necessitating adaptations in healthcare delivery. These include implementing stringent infection control measures, reducing in-person appointments where possible, and increasing the use of telemedicine. Healthcare providers have had to adjust their clinical workflows and care delivery models to ensure patient and staff safety while maintaining the quality of care.14,15

Despite these challenges, the benefits of a multidisciplinary approach in COVID-19 care are substantial. It allows for a comprehensive assessment of patients' needs, enabling the development of coordinated and personalized treatment plans. This holistic approach is particularly valuable in addressing both the acute and long-term effects of COVID-19, ultimately leading to improved patient outcomes and quality of care.

Conclusion

COVID-19 continues to present a complex and evolving global health challenge, with diverse impacts across respiratory, cardiovascular, and other bodily systems, as well as varied clinical severity. Despite the success of vaccination campaigns, which have significantly reduced severe cases and mortality, COVID-19 remains a significant threat, particularly to high-risk populations. Recent treatment advancements, including antivirals, corticosteroids, IL-6 and JAK inhibitors, have proven essential in managing acute and severe cases, while the pandemic has underscored the importance of multidisciplinary approaches in addressing both immediate and long-term health effects. With continued monitoring of variant trends and sustained public health efforts, these combined strategies aim to mitigate the virus's impact while promoting recovery and resilience in affected individuals worldwide.

References

1.         CDC. About COVID-19. COVID-19. September 18, 2024. Accessed October 24, 2024. https://www.cdc.gov/covid/about/index.html

2.         World Health Organization. Coronavirus disease (COVID-19). Accessed October 24, 2024. https://www.who.int/news-room/fact-sheets/detail/coronavirus-disease-(covid-19)

3.         CDC. COVID Data Tracker. Centers for Disease Control and Prevention. March 28, 2020. Accessed October 24, 2024. https://covid.cdc.gov/covid-data-tracker

4.         Mayo Clinic. Coronavirus disease 2019 (COVID-19) - Symptoms and causes. Mayo Clinic. Accessed October 24, 2024. https://www.mayoclinic.org/diseases-conditions/coronavirus/symptoms-causes/syc-20479963

5.         FDA. Commissioner O of the. COVID-19 Test Basics. Published online August 9, 2024. Accessed October 24, 2024. https://www.fda.gov/consumers/consumer-updates/covid-19-test-basics

6.         Hayden MK, Hanson KE, Englund JA, et al. Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing. Infectious Diseases Society of America 2023; Version 3.0.0. Available at https://www.idsociety.org/practice-guideline/covid-19-guideline-diagnostics/. Accessed October 25, 2024.

7.         Mary K Hayden, Ibrahim K El Mikati, Kimberly E Hanson, et al. Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing, Clinical Infectious Diseases, 2024;, ciae121, https://doi.org/10.1093/cid/ciae121

8.         Hayden MK, Hanson KE, Englund JA, et al. Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Antigen Testing. Infectious Diseases Society of America 2022; Version 2.0.0. Available at https://www.idsociety.org/practice-guideline/covid-19-guideline-antigen testing/. Accessed October 25, 2024.

9.         ID Society. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Accessed October 25, 2024. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/

10.       Price E, Hollis N, Salganik J, et al. Implementing a Multidisciplinary Post-COVID Clinic in a Small Community Environment. Arch Rehabil Res Clin Transl. 2023;5(3):100270. doi:10.1016/j.arrct.2023.100270

11.       Lo Bianco G, Di Pietro S, Mazzuca E, et al. Multidisciplinary Approach to the Diagnosis and In-Hospital Management of COVID-19 Infection: A Narrative Review. Front Pharmacol. 2020;11. doi:10.3389/fphar.2020.572168

12.       Physiopedia. The Multidisciplinary Team and COVID-19. Accessed October 25, 2024. https://www.physio-pedia.com/The_Multidisciplinary_Team_and_COVID-19

13.       Squillace N, Cogliandro V, Rossi E, et al. A multidisciplinary approach to screen the post-COVID-19 conditions. BMC Infect Dis. 2023;23(1):54. doi:10.1186/s12879-023-08006-4

14.       Faghy MA, Maden-Wilkinson T, Arena R, et al. COVID-19 patients require multi-disciplinary rehabilitation approaches to address persisting symptom profiles and restore pre-COVID quality of life. Expert Rev Respir Med. 2022;16(5):595-600. doi:10.1080/17476348.2022.2063843

15.       Nguyen HB, Mulpuri N, Cook D, et al. The Impact of COVID-19 on Multidisciplinary Care Delivery to Children with Cerebral Palsy and Other Neuromuscular Complex Chronic Conditions. Children. 2023;10(9):1555. doi:10.3390/children10091555