COVID-19: Current Practice Guidelines

Since its first reported case in Wuhan, Hubei Province, China, the Coronavirus disease 2019 (COVID-19) has had a massive effect on the global economy, crumbling regional financial outlook and posing a continuous challenge to global healthcare. The catastrophic consequences of this highly contagious viral illness have since been documented in the world demographics, with about seven million deaths reported as of August 2024 (World Health Organization [WHO], n.d.). On March 11, 2020, The WHO declared COVID-19 a global pandemic, prompting the initiation of different clinical investigations and surveys focused on the presentation, diagnosis, transmission mode, and potential therapy options for the disease. Early results created substantial progress in understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), limiting its spread, and developing experimental drug candidates for treatment.

However, like other ribonucleic acid (RNA) viruses, SARS-CoV-2 expressed increased episodes of genetic evolution with the development of mutant variants while adapting to human hosts. In the United States, the Center for Disease Control and Prevention (CDC) uses "genomic surveillance to track emerging SARS-CoV-2 variants that cause COVID-19" (CDC, 2024a, pg. 2). SARS-CoV-2 is continually adapting to its milieu. The WHO names new coronavirus variants using Greek alphabet letters. The Public Health Emergency ended in the United States on May 11, 2023 (Assistant Secretary for Public Affairs [ASPA], 2023), but the virus continues to mutate and spread. Currently, there are five variants (Alpha, Beta, Gamma, Delta, and Omicron), with more than 90 subvariants that have been described so far. The numbers continue to climb on a weekly basis, indicating a continued need to update the global community on the current guidelines for the prevention, diagnosis, and management of COVID-19 (Rupp, 2024). This course is designed to bridge the gap between optimal clinical management of COVID-19 and the recent research discoveries on the disease.

Bella Stones lived a long, healthy life, traveling around the globe on a mission after retirement. As a 68-year-old American who had worked 25 years in investment banking, Bella sure had a repository of cash to finance her trips and sight-seeing missions. All was well until March 13th, 2020. Bella was stuck in China as authorities grounded all outgoing flights as an emergency directive to curb the transmission of the recently described COVID-19 infection. Bella had just five days left on her China visit when this happened. Trapped in China, Bella continued her mission, relishing the culture and enjoying a much-needed vacation. A week later, tragedy struck.

Bella had reported to the private clinics of the Metropolitan Hotel and Resort with complaints of fever and generalized body weakness. Dismissing Bella's fears, the nursing assistant administered a shot of intravenous paracetamol. Four days later, Bella was admitted into the examination room of the resort clinic after she was found unconscious in the hotel lobby. Her body temperature peaked at 39.4 degrees Celsius with variable symptoms of shortness of breath, cough, expectoration, and limb weakness.

Her response to automatic coordination and reflex was also slow. Two days before presentation, she had developed diarrhea marked with about 5-6 stools per day. By coordinating with her healthcare insurance provider in Texas, the resort physicians established Bella's medical history of type 2 diabetes, dyslipidemia, and cirrhosis. Bella's vital signs report documented an oxygen saturation of 81%, a pulse of 100 beats/min, a respiratory rate of 27 breaths per minute, and hyperactive bowel sounds. A few hours later, Bella had also developed clinical signs suggestive of fatigue, headache, and myalgia.

Further examinations revealed labored breathing sounds and audible wet murmurs in the lungs. The abdominal architecture was normal, with no lumps or pain. In line with China's guidelines for patients admitted with low oxygen saturation and high body temperature, the physician ordered a computed tomography (CT) scan of the chest, considering the possibility of a COVID-19 infection. CT examination revealed bilateral pneumonia with multiple patches or ground glass appearance. Further investigations were conducted with a nucleic acid amplification test confirming the involvement of influenza A and B in Bella's illness.

A blood panel examination was ordered. The result demonstrated a considerable reduction in the normal counts of red blood cells: 2.53 × 10¹² cells/liter (L); peripheral blood hemoglobin: 72 grams (g)/L; white blood cells: 0.69 × 10⁹ cells/L; lymphocytes: 0.22 × 10⁹ cells/L; and platelets: 41 × 10⁹ cells/L. The neutrophil count was elevated at 0.65 × 10⁹ cells/L. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were 121 millimeters (mm)/hours (hr) and 71.3 milligrams (mg)/L, respectively.

Considering the clinical parameters obtained and Bella's history of close contact with suspected COVID-19 cases some weeks before presentation, the attending physician ordered a COVID-19 test. Blood and saliva specimens were collected and sent to the lab. A few hours later, lab results confirmed that Bella had tested positive for the SARS-CoV-2 virus. She was immediately admitted and isolated for further treatment. On the following days of admission, Bella was administered doses of antiviral medications, including ritonavir and lopinavir. She has also been prescribed methylprednisolone sodium succinate, moxifloxacin hydrochloride sodium chloride injections, pantoprazole enteric-coated tablets, thymosin, and human immunoglobulin.

A regimen of montmorillonite powder and loperamide hydrochloride was also initiated to manage her diarrhea. Bella would eventually report a reduction in the severity of the symptoms some days later. Her diarrhea subsided, her body temperature had dropped to 38.1 degrees Celsius, and her cough had stopped. However, repeated CT scans showed no improvement in bilateral pneumonia, and the level of blood cells showed no improvement.

Despite symptomatic improvement, Bella retested positive for the virus. As with many other cases, Bella was further started on an antiviral therapy regimen to last a few weeks before another test could be ordered.

The history of the world, no matter how the narrative is told, will always include happenings recorded in December 2019. That month, a series of respiratory infections ravaged the city of Wuhan in the Hubei Province of China. At first, a few hundred Wuhan residents were admitted because of respiratory distress and other clinical signs suggesting pneumonia and metabolic disorders. Weeks later, things escalated quickly, with the first thousand reported admission cases. The primary cause of these strange admissions was largely unknown during this period. However, the symptomatic profile of these patients was similar in nature and occurrence to confirmed cases of Middle East respiratory syndrome (MERS) several years ago.

The recurrent themes in the clinical symptoms first described by Wuhan include high-grade fever, productive cough, chest discomfort, severe dyspnea, bilateral lung infiltration, persistent diarrhea, and other clinical indications of pneumonia (Alafif et al., 2022). Preliminary investigations found a link between the first reported cases and the Huanan Seafood Wholesale Market, a wet market in downtown Wuhan famous for its wares of seafood, poultry, wildlife, and live animals. On December 31, 2019, the Wuhan Municipal Health Commission notified the public and made an official report to the WHO on an outbreak of pneumonia.

The 'pneumonia outbreak' was immediately scrutinized because of its similar symptomatology with MERS. RNA sequencing and examining viral particles found that the 'pneumonia outbreak' was caused by a novel beta coronavirus (Wang et al., 2024). In January 2020, independent confirmations of this report were published, igniting a chain reaction of events that would forever change the world. A few months later, thousands of cases were identified in patients with no primary or secondary contact history with Wuhan's Huanan Seafood Wholesale Market.

Clusters of infections were also reported in Europe, North America, Australia, and Africa. Authorities began tracking suspected cases and eventually instituted a lockdown procedure to reduce the transmission rate. Late in February 2020, the International Committee on Taxonomy of Viruses named the novel beta coronavirus isolated from the bronchoalveolar lavage fluid samples of admitted patients as 'SARS-CoV-2,' and the disease itself was called Coronavirus Disease 2019 or COVID-19.

Recent pathogenesis data on SARS-CoV-2 interaction in humans and other primates suggest a median incubation period of 5.1 days for the virus. Host reaction and the first signs of infections are expected to develop within 11.5 days of infection (Leng et al., 2022). Patient evaluation for the confirmation of severity and viral strain can be completed within this timeframe. Evaluation should include a detailed clinical history focused on underlying comorbidities, travel history, possible exposure to confirmed COVID-19 cases, duration of symptoms, and drug history. The current CDC guideline on evaluation prescribes rapid SARS-CoV-2 testing for patients presenting with atypical clinical signs of COVID-19. These include malaise, myalgia, loss of taste, cough, sore throat, generalized body weakness, and fever. Other patients with a known history of possible high-risk exposure should also be evaluated and tested for SARS-CoV-2, even when typical symptoms are absent.

As expected, the first case of human-human transmission of the SARS-CoV-2 virus was first reported in Wuhan, China, after the outbreak. Human-human transmissions reportedly occurred in family clusters, meat-packing plants, migrant worker communities, and crowded settlements. Comparative studies later demonstrated how the virus is more transmissible than SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), and other viruses of the coronaviridae family. The unique virological features and pathogenesis of the SARS-CoV-2 virus contribute to its transmissibility. Viral-laden droplets expelled by face-to-face exposure during talking, coughing, and sneezing are considered the primary mode of SARS-CoV-2 transmission. Exposure time and the viral load in expelled droplets primarily influence the rate of transmissibility.

Prolonged exposure to infected individuals within six feet for at least 15 minutes has been linked with a high risk of transmission (Enabulele & Mobolaji, 2022). However, briefer exposure to asymptomatic patients is less likely to cause transmission. In many patients, the volume of active SARS-CoV-2 viral particles is highest at the time of symptom onset. Viral shedding and, consequently, viral transmission begins about 2-3 days before symptom onset. During this timeframe, both asymptomatic and symptomatic carriers can transmit the virus. Pharyngeal shedding is exceptionally high during the first week of infection, even before symptoms onset, meaning patients can effectively transmit the virus before they get ill.

The SARS-CoV-2 virus can also be transmitted in aerosol particles suspended in the air. These particles can linger for a long time in the air before unsuspecting individuals inhale them. Viral particles in the aerosol penetrate deep into the lung, initiating a cyclic process that ends in a viral invasion of the alveolar cells (Sussman et al., 2022). Research evidence also demonstrates the spread of the virus via inanimate and impermeable surfaces. SARS-CoV-2 can reportedly survive on these surfaces for up to 3-4 days after inoculation. This evidence provides a logical explanation for the rapid spread of COVID-19 in crowded public and hospital spaces. Although face-to-face contact exposure to viral droplets is considered the primary mode of transmission, objects such as a doorknob, cutlery, and clothing used by infected people also seem to contribute to SARS-CoV-2 spread on a larger scale (Kurver et al., 2022).

An increasing body of clinical evidence demonstrates how maternal COVID-19 cases may be associated with vertical transmission of the virus via the transplacental route. However, there are controversial reports about this transmission mode. The probability and risk of vertical transmission seem to depend on multiple factors, including the variant of SARS-CoV-2. In many cases of maternal COVID-19, maternal infection mainly occurs during the third trimester of pregnancy (Wang & Dong, 2023).

As the pandemic ravaged, multiple types of research were initiated to develop and experiment with therapeutic options. Since the development of novel drugs may take years, the focus of these researchers was to identify possible treatment options using approved and currently marketed drugs. Drug repurposing was considered the best approach to finding an effective treatment within a limited time. Multiple clinical trials were launched, testing the virus's effects on antiviral, anti-inflammatory, and anticoagulants. In addition to single-drug trials, combinations were also explored in clinical investigations to provide supportive care and disrupt the normal cycle of viral pathogenicity in infected individuals.

All currently authorized therapy strategies are designed to either alter the cycle of viral replication at the early stage of infection or control the hyperinflammatory states and the coagulation system activation. The CDC updated guidelines on treatment strategies for COVID-19 and authorized the use of antiviral therapies, anti-SARS-CoV-2 neutralizing antibody products, immunomodulatory agents, and Janus kinase (JAK) inhibitors.

As an RNA virus, the SARS-CoV-2 is prone to rapid genetic evolutions, developing multiple mutant variants in the human host. The mutant strains of the virus are expected to exhibit different morphological characteristics and pathogenicity. Compared to the ancestral strain, variations in the pathogenicity of mutant strains are linked to possible changes in the normal cycle of viral entry, replications, and shedding. Since the beginning of the pandemic, five SARS-CoV-2 variants of concern (VOC) have been described. VOCs have a high potential to cause enhanced transmissibility. They can also evade detection, exhibit resistance to established therapies, decrease vaccine effectiveness, or resist antibody neutralization effects. The SARS-CoV-2 VOCs include the Alpha, Beta, Gamma, Delta, and Omicron variants.

In addition to Alpha and other VOCs, the WHO has also described variants of interest (VOIs). VOIs have specific genetic markers linked with modifications that may enhance virulence or transmissibility, decrease the effects of authorized therapies, reduce the efficacy of antibodies obtained by vaccination or natural infection, and increase the virus' ability to evade detection. The eight recognized variants of interest include Epsilon (B.1.427 and B.1.429); Lambda (C.37); Mu (B.1.621); Theta (P.3); Iota (B.1.526); Kappa (B.1.617.1); Zeta (P.2); and Eta (B.1.525).

Vaccination is considered the most effective long-term strategy for preventing and controlling COVID-19. As of October 2020, more than 170 vaccine candidates for COVID-19 were reported, with about 51 of these candidates in different human clinical trial phases. As of April 2022, eight vaccines had the WHO's Emergency Use Authorization (EUA). These vaccines use three different technologies in their composition. These include the mRNA-based vaccines using a selected modified sequence of spike protein gene mRNA‐1273 (Moderna) and the BNT162b2 (BioNTech/Pfizer); the non-replicating adenovirus vector-based DNA vaccines (AZD1222/ChAdOx1 [Oxford/AstraZeneca], JNJ‐78436735/AD26.COV2.S [Janssen/Johnson & Johnson], and the inactivated virus vaccines (CoronaVac [Sinovac Biotech] and BIBP‐CorV [Sinopharm] (Upreti & Samant, 2022).

As of September 2024, the CDC guideline on vaccines and vaccination strategies only recognized three COVID-19 vaccines approved by the FDA under the Emergency Use Authorization (EUA) and the Biologics License Application (BLA) schedules (CDC, 2024b). These vaccines included:

Novavax, a COVID-19 vaccination that has been granted EUA in the United States for the 2024 updated version (United States FDA, 2024), is only authorized in clients aged 12 and older. For individuals who have never been vaccinated, two doses three weeks apart are recommended. For individuals who have had a prior COVID-19 vaccine series, a single dose of Novavax 12 months after the last COVID-19 vaccine is recommended (United States FDA, 2024).

The current CDC guideline also recommends an mRNA vaccine (Pfizer or Moderna) for primary and booster vaccination in all populations. Pemivibart (Pemgarda) is a monoclonal antibody for people who are moderately or severely immunocompromised (CDC, 2024b). Clients who receive this pre-exposure preventative treatment must meet strict FDA-authorized conditions and understand that pemivibart (Pemgarda) is not a replacement for COVID-19 vaccination (CDC, 2024b). The vaccination schedules recommended by the CDC categorize the population into two groups: people who are moderately or severely immunocompromised and those who are not moderately or severely immunocompromised. In all cases of vaccination, an age-appropriate vaccine should be selected based on the recipient's age and the day of vaccination.

SARS-CoV-2 entry into host cells has been linked with multiple organ dysfunctions and general body illnesses. In patients with pre-existing medical conditions, including diabetes, chronic kidney diseases, and cardiovascular diseases, the risk of developing a systemic illness or long-term complications of COVID-19 is higher. In this population, the most reported complications of COVID-19 include multiple organ failure, acute respiratory failure, and sudden clinical deterioration. In the long term, there is an increased risk of myocardial infarction, deep venous thrombosis, arterial thrombosis, and ischemic strokes (Katsoularis et al., 2022). Cardiogenic shock, malignant arrhythmias, and cardiomyopathies have also been reported. Acute renal failure is another long-term complication of COVID-19 linked with a high risk of mortality (Sabaghian et al., 2022).

Collating data from collaborative studies on COVID-19 reveals dysfunctional/delayed bladder emptying as a common long-term neurologic complication. Other prominent ones include ptosis, mild residual peripheral neuropathy, and facial weakness (Valderas et al., 2022). A post-viral cough lasting for about eight weeks has been reported as a common pulmonary complication of COVID-19. Chest tightness, difficulty in breathing, and rhinorrhea have also been reported in children (Borch et al., 2022). Nausea, abdominal pain, and vomiting are the most reported gastrointestinal complications. Multisystem inflammatory syndrome in children (MIS-C) has also been reported in many cases. Researchers have reported a high incidence of major depressive disorder as a common psychiatric complication in adolescents. Other findings have also reported anxiety, avoidance, arousal, and consistent flashbacks in many patients. In patients with an onset of COVID-19 complications, clinical support is recommended.

Frank Doyle, a 42-year-old Caucasian male, previously healthy with no significant past medical history, contracted COVID-19 in December 2020. He experienced moderate symptoms, including fever, fatigue, and loss of taste and smell, and recovered at home without the need for hospitalization. However, months after his acute illness, he began experiencing a range of persistent symptoms that ultimately led to a diagnosis of Long COVID-19. Among these symptoms, he developed psychosis, which became the most concerning aspect of his condition.

Presenting Complaints: In June 2021, approximately six months post-infection, Frank Doyle began to notice cognitive difficulties, including memory lapses and difficulty concentrating. He also reported persistent fatigue, shortness of breath, and occasional heart palpitations. By July 2021, his mental health symptoms had worsened. He described experiencing vivid and disturbing hallucinations, both auditory and visual. He began to experience paranoia, believing that he was being watched and that people were plotting against him, despite no evidence to support these beliefs.

Medical History: Mr. Doyle had no prior history of mental illness, including psychosis, depression, or anxiety. He had no history of substance abuse and was not taking any medications regularly before contracting COVID-19. His family history was negative for psychiatric disorders.

Clinical Examination: Upon examination, Mr. Doyle appeared anxious and somewhat agitated. He was oriented to person, place, and time but had a markedly paranoid affect. He described hearing voices that were not present and seeing shadowy figures that he believed were following him. His physical examination was unremarkable, with no neurological deficits noted.

Investigations:

• Blood Tests: Routine blood work, including complete blood count, liver function tests, and thyroid function tests, were within normal limits.
• Neuroimaging: Magnetic resonance imaging (MRI) of the brain showed no structural abnormalities.
• Electroencephalogram (EEG): Normal, with no evidence of epileptiform activity.
• Psychiatric Assessment: A full psychiatric evaluation confirmed the presence of paranoid delusions and hallucinations consistent with psychosis.

Mr. Doyle was diagnosed with Long COVID-19, with a significant neuropsychiatric complication in the form of psychosis. This was classified as post-COVID-19 psychosis, a rare but increasingly recognized manifestation of Long COVID-19.

Mr. Doyle was started on the atypical antipsychotic medication, olanzapine, at a low dose, which was gradually titrated based on his response and tolerance. He also received supportive psychotherapy to help him cope with the distress caused by his symptoms. His treatment plan included regular follow-up with a psychiatrist and close monitoring for any potential side effects of the medication.

In addition to his psychiatric treatment, Mr. Doyle was referred to a multidisciplinary Long COVID-19 clinic, where he received comprehensive care for his other lingering symptoms, including fatigue and cognitive impairment. His treatment included graded exercise therapy, cognitive-behavioral therapy, and nutritional support to address his overall health.

Over the course of several months, Mr. Doyle's psychotic symptoms gradually improved with medication. His hallucinations became less frequent and less intense, and his paranoid delusions subsided. However, he continued to experience mild cognitive difficulties and fatigue, which were managed through ongoing therapy and lifestyle modifications.

This case highlights the complex and multifaceted nature of Long COVID-19, particularly its potential to affect mental health. While respiratory and cardiovascular symptoms are more commonly reported, neuropsychiatric symptoms such as psychosis, though rare, can have a profound impact on a patient's quality of life. The exact pathophysiology underlying post-COVID-19 psychosis remains unclear, but it is hypothesized to involve direct viral effects on the brain, immune-mediated mechanisms, and the psychological trauma of prolonged illness and isolation.

Early recognition and intervention are crucial in managing post-COVID-19 psychosis. A multidisciplinary approach involving mental health professionals, primary care providers, and specialists in Long COVID-19, is essential to address the full spectrum of symptoms and improve patient outcomes.

Mr. Doyle's case underscores the importance of considering neuropsychiatric complications in patients with Long COVID-19. This case study also highlights the need for further research into the neuropsychiatric sequelae of COVID-19 to develop more effective treatment strategies and improve patient care.

SARS-CoV-2 and its variants have wreaked havoc in different parts of the world, resulting in deaths and disabilities. Until a large percentage of the global population is vaccinated, the SARS-CoV-2 virus and its variants will remain a considerable threat to global healthcare systems. As it stands, enforcing the CDC prevention strategies and ensuring age-appropriate vaccination using the right vaccines are the best approach to curbing the spread of this virus. While the search for more vaccines and a cure continues, clinical providers are encouraged to adopt a holistic care plan that prioritizes prevention, patient education, and supportive care. Clinicians are also expected to maintain a high index of suspicion in individuals with prior exposure to symptomatic or asymptomatic patients and those from a high-risk region.

To change the pandemic's dynamic, community clinics and support centers should be well-equipped to triage moderate and high-risk patients, using the approved guidelines on patient examination and therapy selection. Continued viral surveillance should be performed at regular intervals to ascertain the level of risk posed by new variants of the virus. The importance of public education on symptom presentation and available vaccine options should not be undermined. Adopting this multi-pronged approach toward this viral disease goes a long way in eliminating the virus and maintaining a healthy global population.

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