Prevention

This part focuses on prevention of COVID-19 infection. Based on research findings, control measures and best and worst practices in response to the COVID-19 pandemic are considered.

A paper by Bahl and colleagues (2022) showed that SARS-CoV-2 can be detected in the air and remains viable 3 hours after aerosolization. The transmission of COVID-19 is similar to SARS, which can spread through contact, droplets, and airborne routes. Airborne transmission is possible due to the presence of viral loads in the respiratory tract and the persistence of the virus in the air. They suggest precautions against airborne dispersal for the occupational health and safety of health workers treating patients with COVID-19 (Bahl et al. 2022).

A survey conducted online with over 2000 adults living in North America and Europe aimed to study the adherence rates and factors influencing compliance with social distancing recommendations during the early stages of the pandemic. The results showed that people’s adherence to these recommendations varied significantly among individuals and may depend on the specific actions they are being asked to take. The most effective factors that promoted adherence to social distancing guidelines include a desire to safeguard oneself, a sense of responsibility to protect the community, and the ability to work or study remotely. The most significant obstacles to compliance were having friends or family who required assistance and a need for social interaction to avoid feelings of isolation. To enhance adherence to social distancing measures, future interventions should combine personalized approaches aimed at overcoming the identified barriers with institutional measures and public health interventions (Coroiu et al. 2020).

Identifying secondary cases before the onset of infection by setting up quarantine and testing is a prevention measure that was heavily invested in during the early stages of the COVID-19 pandemic by developing digital contact tracing apps. However, the international experience of digital contact tracing apps during the COVID-19 pandemic demonstrated how challenging their design and deployment are, including ethical issues such as data protection and privacy. In this field, there is potential for promising advancements through the integration of blockchain technology, ultra-wideband technology, and artificial intelligence in app design (O’Connell et al. 2021).

In vaccination campaigns, prioritization of certain population groups can influence the success of the campaign itself. A study which evaluated the vaccine allocation in Rhode Island and Massachusetts found that allocating a substantial proportion of vaccine supply to individuals at high risk of mortality is an effective strategy for reducing total cumulative deaths. The study suggests that a median of 327 to 340 deaths could be avoided in Rhode Island by optimizing vaccine allocation and vaccinating the elderly first. While the study focused on individuals over the age of 70, the results could be applied to other high-mortality groups (i.e., obesity, diabetes, past lung disease, lack of healthcare access) by allocating a higher proportion of vaccines to them. However, it is important to note that the study did not explicitly model other high-mortality groups, so the results would need to be interpreted with caution. In addition, individuals who have high-contact rates with high-mortality risk groups or cohabit with them should similarly be prioritized for vaccination. Though, vaccination of only high-contact groups cannot be considered as one of the best practices, mainly due to the wide mortality differences between the youngest and oldest age groups (Tran et al. 2021).

Treatment/care

Patients with a SARS-CoV-2 infection can experience a wide range of clinical manifestations, ranging from no symptoms to critical illness. Common symptoms include fatigue, fever, cough, loss of smell or tasting, and headache, among others. In addition, approximately 30% of patients also reported gastrointestinal symptoms such as diarrhea, nausea, and stomach pain (Struyf et al. 2022).

In general, adults with SARS-CoV-2 infection can be grouped into five severity categories (Struyf et al. 2022):

Asymptomatic or pre-symptomatic infection, positive test for SARS-CoV-2 but no symptoms consistent with COVID-19.

Mild illness, individuals who have any of the various signs and symptoms of COVID-19 (e.g., fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell) but do not have shortness of breath, dyspnea, or abnormal chest imaging.

Moderate illness, evidence of lower respiratory disease during clinical assessment or imaging and oxygen saturation ≥ 94% on room air at sea level.

Severe illness, previous listed symptoms, breathlessness, and increased respiratory rate which may indicate pneumonia and oxygen need.

Critical illness, individuals who have respiratory failure, septic shock, and/or multiple organ dysfunction requiring intensive support (Struyf et al. 2022).

It is important to differentiate between these conditions because they require different patient management. Therefore, there are three targets for current SARS-CoV-2 infection:

Asymptomatic or symptomatic infection of any severity.

Mild or moderate COVID-19 disease.

Severe or critical COVID-19 pneumonia (Struyf et al. 2022).

Bellino (2022) reported that most COVID-19 patients experience mild to moderate symptoms and can recover without needing special treatment. However, up to 15% of patients may develop severe or critical symptoms. Even though vaccination has significantly reduced the number of COVID-19 cases, hospitalizations, and deaths, managing severe cases remains a challenge due to the multisystemic nature of the infection, which can affect several body systems. This was especially true during the first stages of the pandemic, during which, due to the lack of specific preventive and therapeutic measures, various pre-existing medications were used "off-label" for the treatment of patients infected with SARS-CoV2. COVID-19 has been treated with antivirals, immunomodulators, antibiotics, stem cells, plasma therapy, and others (Oliver et al. 2022). Each of these treatment methods had benefits and drawbacks, and their effectiveness varied depending on the specific medication, the severity of the disease, and the stage of the illness. In summary, as reported in a review of Haddad and colleagues (Haddad et al. 2022), some antiviral agents, such as remdesivir, ivermectin, and lopinavir have shown some effectiveness in reducing the duration of hospitalization and improving clinical outcomes in hospitalized patients with severe COVID-19.

Corticosteroids usage, such as dexamethasone, is supported by robust evidence and has been shown to reduce mortality in critically ill COVID-19 patients. However, the use of other medications, such as immunomodulatory and anti-inflammatory drugs (Tocilizumab, sarilumab, Chloroquine) is quite conflicting. Moreover, conflicting data are present on the usage of convalescent plasma and vitamin D (Haddad et al. 2022). In Table 2, findings on other medications and their efficacy are reported. Subsequent randomized studies are needed to warrant the determination of their usefulness.

Table 2 Summary of the efficacy of several pharmacologic agents for the treatment of COVID-19 adapted from “A Comprehensive Review on the Efficacy of Several Pharmacologic Agents for the Treatment of COVID-19,” Haddad et al. 2022. For all the listed agents, further randomized studies are necessary to support their usage (Haddad et al. 2022)

In addition, to explore the efficacy of existing drugs, scientists worldwide tried to develop new treatment options, such as new drugs, immunotherapies, and host-directed therapies.

These treatments can be divided into two main categories: those that directly target the virus replication cycle, and those that aim to boost the immune response or reduce inflammation (Jiang et al. 2022). Two main processes are thought to drive the pathogenesis of COVID-19. During the early stages of COVID-19, virus replication was the primary cause of the disease, and drugs such as antivirals were likely to be most effective. These work by preventing the virus from replicating and spreading throughout the body. As the disease progresses, however, the immune response can become dysregulated, leading to excessive inflammation and tissue damage. At this stage, treatments that focus on regulating the immune response or reducing inflammation may be more effective (Treatment Guidelines 2023).

In addition to the drugs discussed, and to the symptomatic treatment of most common clinical manifestations (antipyretics, analgesics, and antitussives for fever, headache, myalgias, and cough), the National Institutes of Health (NIH) guidelines (Treatment Guidelines 2023) suggest holistic patient care, based on the biopsychosocial model. It is so essential to encourage patients to drink fluids regularly to prevent dehydration and rest as needed during the acute phase of the illness. Patients can gradually increase their activity level based on their tolerance. Psychological support is an essential aspect of caring for COVID-19 patients. The pandemic has led to significant levels of stress, anxiety, and depression. Patients with COVID-19 may experience fear, isolation, and uncertainty, which can contribute to their overall psychological distress. Therefore, it is crucial to provide psychological support, as well as video-based therapy in case of lockdowns, to help patients cope with their illness and its associated challenges. Psychological support can include interventions such as counseling, psychotherapy, and cognitive–behavioral therapy, which can help patients manage their emotions, develop coping strategies, and improve their overall mental health. It is also important to provide patients with accurate and clear information about their illness, including its course, treatment options, and prognosis, to reduce anxiety and uncertainty (Karekla et al. 2021).

In conclusion, according to the review by Pandolfi and colleagues (Pandolfi et al. 2022), main aspects of the treatment policy for COVID-19 include the following:

1.

Significance of post-mortem investigations on COVID-19-caused deaths in developing effective treatment protocols in the early stages of the disease based on its etiopathogenesis.

2.

The early treatment of COVID-19 with common painkillers may not effectively address the illness and could even worsen SARS-CoV-2 symptoms in patients.

3.

Importance of having a comprehensive understanding of the demographic composition of each country to implement effective safety procedures for at-risk groups, such as the elderly.

4.

Decentralized medical coverage highly connected in large communities is better than centralized hospitals; in fact, better management of decentralized medical resources could have prevented a significant number of hospitalizations, thereby reducing the mortality rate.

5.

Sharing information, expertise, and skills between physicians and care personnel is crucial to speed up the development of a nationally agreed-upon and successful therapy protocol for COVID-19.

It is important to note that the best timing and combination of treatments for COVID-19 is still being studied, and treatment recommendations may vary depending on the severity of the disease.

Rehabilitation

Many patients with previous COVID-19 infection report persistent symptoms. The National Institute for Health and Care Excellence (NICE) in the UK elaborated three possible conditions after the infection (Pandolfi et al. 2022):

1.

Acute COVID-19, where signs and symptoms of the infection persist up to a maximum of 4 weeks

2.

Ongoing symptomatic COVID-19, where signs and symptoms of the infection last from 4 to 12 weeks

3.

Post-COVID-19 syndrome, in which signs and symptoms that develop during or after the infection are present even after 12 weeks and cannot be explained by an alternative diagnosis (NICE 2020)

Post-COVID symptoms are varied and can affect different organic systems. Therefore, the nature of these symptoms leads to the need of a holistic, tailored, and multidisciplinary rehabilitative intervention plan focused particularly on self-management (NICE 2020). The UK National Health Service (NHS) guidelines propose three models for the management of post-COVID patients according to the severity of the acute infection and on whether the patient has been hospitalized (NHS 2021):

1.

Non-hospitalized patients. A central role in this scenario is played by the general practitioner, who must be adequately trained on the topic of post-COVID rehabilitation to identify those symptoms that may have been caused by the infection and play a connection between patients and needed specialists.

2.

Patients who were hospitalized for COVID-19. These patients should undergo a 12-week post-discharge assessment, comprising chest X-ray and a review of symptoms for an eventual further continuation of the rehabilitation.

3.

Patients who required intensive care unit (ICU) admission. They should undergo a multidisciplinary reassessment at 4–6 weeks post-discharge. If conditions have improved, patients will be treated like other hospitalized individuals (NHS 2021).

WHO has identified the following conditions as the most important sequelae of COVID-19 that may require rehabilitation [Negrini et al. 2022; WHO 2022]:

Fatigue, exhaustion

Breathing impairment

Autonomic nervous system dysfunctions

Post-exertional symptom exacerbation (PESE)

Dysphagia and dysphonia

Arthralgia

Olfactory impairment

Cognitive impairment, such as attention deficit, memory impairment, concentration impairment, executive dysfunction, and cognitive communication disorder

Other psychological disorders: anxiety and depression

Staffolani and colleagues (2022), in their comprehensive narrative review of 2022, revised possible treatments for most of the common post-COVID manifestations. According to this review, for symptoms like pain and myalgia, symptomatic treatment may be used, while for patients with pulmonary or neurologic sequelae, chest physiotherapy and neurorehabilitation are useful. A multidisciplinary approach is recommended for respiratory symptoms, where non-pharmacological strategies such as breathing exercises, pulmonary rehabilitation, and postural relief may be helpful. Cardiovascular symptoms, such as tachycardia, may benefit from treatment with beta-blockers, while myocarditis usually resolves over time. For fatigue and cognitive and neuropsychiatric disorders, self-management, cognitive behavioral therapy, graded exercise treatment, and pacing may be used. Medications such as methylphenidate, donepezil, and modafinil may also be considered. Group therapy and supportive listening can also be effective. Sleep disturbances, post-traumatic stress disorder, depression, anxiety, and other mental health problems must be managed according to specific guidelines. Emerging treatments such as hyperbaric oxygen, breath exercise, and singing are being studied to treat respiratory symptoms of post-COVID. Other adjuvant therapies such as vitamin C, nicotinamide, probiotic supplements, leronlimab, tocilizumab, and melatonin are also being studied. Home-based and community rehabilitation can be delivered through different strategies, such as tele-rehabilitation or direct care (Lugo-Agudelo et al. 2021).