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COVID-19: Current Practice Guidelines (FL Autonomous Practice INITIAL-Pharmacology)

2 Contact Hours including 2 Advanced Pharmacology Hours
Only FL APRNs will receive credit for this course
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This course is only applicable for Florida nurse practitioners who need to meet the autonomous practice initial licensure requirement.
This peer reviewed course is applicable for the following professions:
Advanced Practice Registered Nurse (APRN)
This course will be updated or discontinued on or before Sunday, December 15, 2024

Nationally Accredited

CEUFast, Inc. is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. ANCC Provider number #P0274.

Outcomes

≥92% of participants will understand the current recommendations and guidelines in the overall management of Covid-19.

Objectives

After completing this continuing education course, the learner will be able to:

  1. Recognize the latest updates on the clinical evaluation of COVID-19 patients, SARS-CoV-2 variants, and disease transmission.
  2. Identify the latest recommendations for disease prevention and limiting disease transmission.
  3. Identify the current variants’ unique characteristics and how they affect clinical presentation.
  4. Outline vaccination strategies for COVID-19.
CEUFast Inc. and the course planners for this educational activity do not have any relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.
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COVID-19: Current Practice Guidelines (FL Autonomous Practice INITIAL-Pharmacology)
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Author:    Jassin Jouria (MD)

Introduction

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 6 million deaths reported as of March 2022. On March 11, 2020, The World Health Organization 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 SARS-CoV-2, limiting its spread, and developing experimental drug candidates for treatment.

However, like other RNA viruses, SARS-CoV-2 expressed increased episodes of genetic evolution with the development of mutant variants while adapting to human hosts. Five variants and more than 15 subvariants of this virus have been described so far. With the recent development, there is an increased need to update the global community on the current guidelines for the prevention, diagnosis, and management of COVID-19. This course is designed to bridge the gap between optimal clinical management of COVID-19 and the recent research discoveries on the disease.

Case Study

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 5-days 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 Metropolitan Hotel and Resort 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.

Abdominal 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 on patients admitted with low oxygen saturation and high body temperature, the physician ordered a Chest CT examination 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/l; peripheral blood hemoglobin: 72 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 and C-reactive protein level were 121 mm/hr and 71.3 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. In the following days on 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 symptoms severity 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.

A brief overview of SARS-CoV-2 and COVID-19

The history of the world, no matter how the narrative is told, would 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 admissions 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 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 World Health Organization on an outbreak of pneumonia.

Considering its similar symptomatology with MERS, the 'pneumonia outbreak' was immediately scrutinized. RNA sequencing and examining viral particles found that the 'pneumonia outbreak' was caused by a novel betacoronavirus (Xiang et al., 2022). 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 betacoronavirus isolated from the bronchoalveolar lavage fluid samples of admitted patients as 'SARS-CoV-2,' and the disease itself was called Coronavirus Disease 2019 (COVID-19).


timeline

Fig. 1: Timeline of key events of the COVID-19 outbreak (Hu et al., 2021)

Coronaviruses; Taxonomy, Discovery, and Spread

The term 'Coronavirus' describes one of the largest genomes of RNA virus ever discovered and studied by humans. A large percentage of the global population may have once been infected by a member of this genome. Coronaviruses have a positively-stranded RNA, with a characteristic crown-like appearance under an electron microscope. As a large family of viruses, the phylotypic and genomic descriptions of these viruses are quite extensive. For instance, the subfamily Orthocoronaviriae is further classified into four different genera, including Alphacoronavirus (alphaCoV), Betacoronavirus (betaCoV), Deltacoronavirus (deltaCoV), and Gammacoronavirus (gammaCoV). On the topic of COVID-19, the Betacoronavirus is of significant interest. Preliminary studies suggest that bats and rodents are the probable gene sources of viruses identified in this subfamily. The characteristic pathological effects of these viruses in humans include dysfunction of the enteric, neurologic, respiratory, and hepatic systems. They are notorious for crossing biological membranes and causing different viral diseases in camels, cattle, cats, and humans (Zhao et al., 2022).

The first group of Human coronaviruses was identified in the mid-1960s. HCoV-OC43, HCoV-HKU1 (betaCoVs of the A lineage); HCoV-229E, and HCoV-NL63 (alphaCoVs) were reported to cause the common cold and upper respiratory tract infections, particularly in immunocompromised humans. Epidemiological studies in the 1970s suggested an estimated 2% global healthy carriers of HCoVs. In these carriers, the resultant respiratory tract infections are usually self-limiting and require no critical care in most cases. Coronaviruses were largely considered harmless in humans until the isolation and identification of 229E and OC43 (Paoletti et al., 2022).

In 2012, the Middle East Respiratory Syndrome coronavirus (MERS-CoV) was identified in humans. The outbreak of MERS-CoV primarily demonstrated the existence of novel, highly pathogenic coronaviruses transmitted from animals to humans with an enormous consequence for global public health. The subsequent outbreak of SARS-CoV-2 in Wuhan, China, affirmed this narrative as the infection took a fatality rate of 10% in the infected population. Between the MERS-CoV in 2012 and SARS-CoV-2 in 2019, the number of identified coronaviruses with possible pathogenic effects in humans has considerably increased.

Although there are still uncleared controversies about where and how the SARS-CoV-2 virus first entered humans, some preliminary investigations have suggested that the Huanan Seafood Wholesale Market may not be the source of the virus. In a 2019 study conducted in France, researchers detected virus samples in pneumonia patients using PCR. This study suggested an early spread in France before the global transmission was traced to China (Li et al., 2022). To resolve the issues on the origin of this virus, researchers have initiated retrospective investigations focused on well-validated assays of virus samples isolated from animals and humans.

SARS-CoV-2 Virus; Genomics, Phylogeny, and Taxonomy

The novel SARS-CoV-2 virus shares genotypic similarities with the SARS-CoV and the MERS-CoV. Sequencing studies attribute about 50% of the genomic components of the SARS-CoV-2 virus to MERS-CoV and the other 50% to SARS-CoV (Abdullaev. et al., 2022). Beyond the genomic similarities, proteins encoded by the novel coronavirus also share about 90% amino acid identity with SARS-CoV. Most of the non-structural proteins of the novel virus have also been found to share about 80% amino acid sequence identity with SARS-CoV (Ortega et al., 2022). The similarities in protein sequence and genomic components explain the common pathogenesis and host body characters shared among these viruses.

Structurally, the SARS-CoV-2 virus has 1,273 amino acids and consists of four structural proteins -the nucleocapsid protein (N), Spike protein (S), Membrane proteins (M), and the Envelope protein (E). The nucleocapsid protein forms a helical capsid completely housing the viral genome. The resulting primary structure is further enclosed by a lipid envelope formed by the other three proteins. Individually, these proteins perform different functions in the virus's life cycle, coordinating host recognition, attachment, entry, replication, and pathogenicity. On microscopic examination, the SARS-CoV-2 virus structurally resembles a crown. Spike proteins found on the surface form large protrusions (Peplomers) made of three complex segments; the ectodomain, transmembrane domain, and the intracellular tail (Yan et al., 2022). During an active infection phase, the receptor binding sub-units (S1 and S2) on the ectodomain bind and fuse with the host, creating a membrane channel through which viral particles are released into the host cell.

SARS-CoV-2 structure in graphic

Figure 2

During viral entry, the S1 subunits fuse directly with the sugar and ACE2 receptors (Unione et al., 2022). The S2 subunit changes conformation and assumes a post-fusion state that completes entry into the host cell (Sun et al., 2022). Research results on host cell invasion by SARS-CoV-2 suggest the non-endosomal and endocytic pathways as the main routes of entry (Chakrabarty et al., 2022). In many cases, macrophages can also act as storage for viral particles before entry is completed. These biological entities also provide minimal support for viral replication. Dendritic cells and other immune cells may also serve as transporters for SARS-CoV-2, a move that significantly influences the pathogenesis of the virus.

On binding into the ACE2 cells of the epithelial cells in the human respiratory tract, SARS-CoV-2 replicates and migrates in the airways, ultimately invading the alveolar cells of the lungs. As an initial biological response, alveolar cell invasion may trigger an extensive immune response. With this response pattern, cytokines may trigger acute respiratory distress syndrome and respiratory failure, two of the leading causes of mortality in COVID-19 patients (Latifi-Pupovci et al., 2022). It appears the severity of immune response depends on the immune status, age, and existence of comorbidities. Older patients with pre-existing diseases are more predisposed to developing cytokine storm syndrome that may trigger respiratory stress disorder and multiple organ failure (Kirtipal et al., 2022).

Clinical Presentation and the Evaluation of Suspected COVID-19 Infections

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.

Clinical Evaluation of Suspected COVID-19 Cases

Molecular Testing (RT-PCR)

The current guideline on treatment and evaluation recognizes nasopharyngeal swabs for SARS-CoV-2 nucleic acid using real-time PCR assay as the gold standard of COVID-19 diagnosis. These assays are validated by the US Food and Drug Administration (FDA), calibrated, and designed for the qualitative detection of the SARS-CoV-2 nucleic acid sequence. Specimens can also be obtained from oropharyngeal swabs, anterior/mid-turbinate nasal swabs, nasopharyngeal aspirates, saliva, and bronchoalveolar lavage. Specimen collection using bronchoalveolar lavage is reserved explicitly for mechanically ventilated patients as studies suggest a long-term activity of SARS-CoV-2 in lower respiratory tract samples. In symptomatic and asymptomatic patients, specimen collections should be done under sterile conditions and in a mechanically ventilated environment.

Specimens collected should be stored at 4 degrees Celsius if the immediate analysis is not feasible. In the lab, the sample should be analyzed and processed for the amplification of viral genetic material through the reverse-transcription process (Cascella et al., 2022). A reverse-transcription cycle should include the synthesis of double-stranded DNA from the viral RNA using real-time RT-PCR or reverse transcription PCR (RT-PCR) (Dhar et al., 2022). These cycles reveal conserved portions of the SARS-CoV-2 genetic code in the amplified material. Preliminary studies conducted on the sensitivity of PCR offered controversial results; however, this standard is considered an effective evaluation method under the right conditions. The conditions prescribed for the PCR analysis of specimens directly affect the sensitivity of PCR testing. Factors influencing this sensitivity include specimen source, exposure time, specimen adequacy, and technical specimen collection (Park et al., 2022). FDA-approved SARS-CoV-2 PCR assays should be used as they reportedly produce nearly 100% sensitivity in the absence of zero cross-contamination during specimen collection and processing (Chuange et al., 2022).

Serology Testing and Laboratory Assessments

Compared to molecular testing using PCR assays, serology testing using PCR is less effective. However, serology testing is suitable for broad surveillance of COVID-19. Serology testing commercial kits available today primarily evaluate a sample for the presence of antibodies. The most significant limitation of serology testing is low sensitivity, specificity, and weakly reproducible results. In addition to broad surveillance, public health authorities have also adopted serology testing in evaluating the level of immunity conferred on the population due to infection or mass vaccination. Recently, the CDC announced the production of an antibody test with a specificity reportedly higher than 99% and a sensitivity score of 96% (Cascella et al., 2022). The new test kit can also identify an individual with a history of COVID-19 infection.

Complete blood count offers a comprehensive picture of the metabolic health of the liver, kidneys, and other major organs of the body. As a comprehensive metabolic panel, CBC can suggest viral invasion by producing a quantitative comparison between the blood component count in suspected COVID-19 patients and healthy humans. Other lab assessments may test for inflammatory markers indicating host cell invasion. Inflammatory markers showing viral invasion include ferritin, ESR, D-dimer, C-reactive protein (CRP), lactate dehydrogenase, and procalcitonin (Sen et al., 2022).

Imaging Evaluations

Imaging evaluation should be considered based on the clinical presentations of the patient. Although there are no strict guidelines on imaging modalities of SARS-CoV-2 assessment, imaging studies may provide important information and support for diagnosis, management, and follow-up. Chest computed tomography, lung ultrasound, and chest X-ray may give diagnostic information in the early and later stages of infection.

Chest X-ray

Chest x-rays are poor evaluation options at the early stage of infection. Chest x-ray results of patients at the early stage of infections were completely normal. However, bilateral multifocal alveolar opacities have been observed at the advanced stages. In many patients, pleural effusion was also recorded as the alveolar opacity confluence up to the opacity of the lungs (Moodley et al., 2022).

Lung Ultrasound

This imaging option offers valuable results in tracking the course of disease progression. In the initial stages, ultrasonographic examination of the lung identifies focal interstitial patterns and a 'white lung' at the advanced stage with evidence of subpleural consolidations. In managing COVID-19, lung ultrasounds are helpful in patient follow-up and determining the need for mechanical ventilation. Through the years, the widely reported ultrasonographic features in COVID-19 patients include;

  • Thickened 'Pleural lines' with irregularities and consistent discontinuities that are entirely erratic. The 'Pleural Lines' are in addition to subpleural lesions that appear as nodules or small patchy consolidations.
  • Perilesional pleural effusions.
  • Motionless, calescent 'B lines' with a flowing consistency up to the square of a 'white lung'.
  • Bilateral and posterior field thickenings are prominently visible in the lower fields (D'Ardes et al., 2022).

Clinical Presentations of COVID-19 Patients

Based on the stage of disease progression and the severity, various clinical manifestations have been documented by epidemiological surveys on COVID-19 patients. Clinical symptoms also appear to differ with age (Odada et al., 2022). Older men with comorbidities show a significant probability of developing severe respiratory diseases requiring emergency critical care. The mortality rate is higher in this population. In the young population, the symptoms most likely to be reported are those consistent with cases of mild pneumonia (Panagouli et al., 2022).

In many cases, symptoms were also absent. In pregnant women, there are studies demonstrating the evidence of transplacental transmission of the virus, as the expectant mother manifests mild pneumonia symptoms. In most reported cases of infections, the symptom profile documented includes high-grade fever, cough, dyspnea, anorexia, diarrhea, and fatigue. Others include headache, chest pain, hemoptysis, sore throat, chills, and vomiting. Symptoms of olfactory and taste bud disorders have also been widely reported (Tomasino et al., 2022).

An early report of symptomatic findings in 72,314 cases in China remains the reference study on the clinical manifestation of COVID-19. About 81% of these cases were classified as mild, 14% as severe cases requiring urgent medical intervention, and 5% as critical cases. In critical cases, patients had septic shock, respiratory failure, and multiple organ dysfunctions. As in patients with MERS and SARS, most of the evaluated patients also developed marked lymphopenia and high levels of plasma cytokines. In the general population, epidemiological studies have documented a list of symptoms reported based on severity and organ systems affected.

Gastrointestinal Symptoms

The most commonly reported GI symptoms include nausea, diarrhea, anorexia, and vomiting. Abdominal pains and rumblings are also reported in many patients. In a few cases, portal vein thrombosis and acute mesenteric ischemia have been reported. Studies have reported a similar mortality rate among patients with severe GI symptoms and the overall mortality rate in COVID-19 patients (Zeng et al., 2022).

Renal Symptoms

In COVID-19 patients under intensive care, the risk of kidney injury is significantly increased. Renal complications reported are multifactorial and reflect directly on the cytotoxicity of the SARS-CoV-2 virus. Acute kidney injury is the most critical extrapulmonary manifestation reported in COVID-19 patients. Other important renal manifestations include hematuria, proteinuria, electrolyte imbalance, hyponatremia, metabolic acidosis, and hyperkalemia (Jdiaa et al., 2022).

Hematologic Symptoms

There is clinical evidence of venous and thromboembolic events such as deep venous thrombosis, ischemia, myocardial infarction, and arterial thromboses. In addition, there are marked elevations of fibrinogen levels, prothrombin time, D-dimer level, and partial thromboplastin time. These elevations give a logical validation for the hematological abnormalities reported in COVID-19 patients. Hematologic manifestations include lymphopenia, thrombocytopenia, elevated ESR levels, leukopenia, and leukocytosis (Al-Saadi EAKD et al., 2022).

Cardiac Symptoms

The burden of pre-existing cardiovascular diseases significantly influences the cardiac symptoms reported by COVID-19 patients. Meta-analysis research understudying this link has reported a significant risk of ICU admission and mortality in COVID-19 patients with myocardial injury. These injuries manifest as myocarditis and myocardial ischemia. Elevated troponin levels also predisposed these patients to frequent malignant arrhythmias and a high rate of mechanical ventilation. Other important cardiac manifestations of the SARS-CoV-2 virus include cardiomyopathy, cardiogenic shock, and acute coronary syndrome (Basu-Ray et al., 2022).

Cutaneous Symptoms

Based on the result of multiple meta-analyses studying the effects of SARS-CoV-2 virus invasion on cutaneous cells, acral lesions appearing as pseudo chilblain are considered the most common cutaneous manifestation in COVID-19 patients. Unlike in other organ systems, the development of specific cutaneous symptoms seems to depend primarily on the patient's age. Other reported manifestation includes erythematous maculopapular, vesicular, and urticarial rashes and erythematous multiform-like eruptions (Sodeifian et al., 2022).

Neurologic Symptoms

Neurologic symptoms are commonly reported in the advanced stages of infection. Impairment of consciousness, seizures, ageusia, and anosmia are widely reported. Others include toxic metabolic encephalopathy, stroke, and headache. Recently, Guillain-Barré syndrome (GBS) was reported in an epidemiological study conducted in Northern Italy (Blanco et al., 2022).

Modes of Transmission

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, 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 6 feet for at least 15 minutes has been linked with a high risk of transmission (Enabulele et al., 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 symptoms 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 to 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).

There is an increasing body of clinical evidence demonstrating 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 et al., 2022).

Current Treatment Options

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 aimed at providing supportive care and disrupting 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 guideline on treatment strategies for COVID-19 authorized the use of antiviral therapies, anti-SARS-CoV-2 neutralizing antibody products, immunomodulatory agents, and Janus kinase inhibitors.

Antiviral Therapies

Remdesivir

Remdesivir, a broad-spectrum antiviral agent, was the first drug approved by the Food and Drug Administration to treat COVID-19. The high point in Remdesivir as an antiviral agent is its capacity to inhibit the effects of SARS-COV-2 as an RNA-dependent RNA polymerase. It inhibits the rapid replications of the virus in the host cell. Since its approval, Remdesivir has been used in different clinical trials to evaluate its efficacy, safe dosage regimen, and adverse effects in special populations. In many of these studies, an improved clinical outcome was reported; however, contrasting evidence has also been reported. Contrasting findings were mainly due to a small number of randomized trials, genetic reasons, different therapy regimens, and varied study designs. Currently, the use of Remdesivir is only approved in adults and pediatric patients aged 12 and above and weighs at least 40 kg. The recommended dosage regimen is 200 mg IV, then 100 mg IV does administer daily over 4 days. If the well-tolerated in the first 4 days and there were no significant clinical improvements, therapy duration may be extended to 10 days.

In addition to body weight and patient, the safe use of Remdesivir also involves an evaluation of the disease severity. In moderate infections, no sufficient evidence recommends the use of Remdesivir. However, Remdesivir is appropriate for severe infections and in patients with a high risk of disease progression. The current CDC guideline also recommends a Remdesivir regimen in hospitalized patients requiring supplemental oxygen without a ventilator or any other device. In a recent randomized, double-blind placebo-controlled trial published by the New England Journal of Medicine, researchers reported an 87% lower risk of hospitalization or death in at-risk patients treated with a 3-day course of Remdesivir (Gottlieb et al., 2022).

Paxlovid

Paxlovid, a combination of ritonavir and nirmatrevil, was first authorized by the FDA on December 22, 2021, for the treatment of mild to moderate COVID-19. Designed as an oral combination of two pills, the phase 2-3 data report of the interim analysis of Paxlovid was promising. The study, which included a participant pool of 1219 patients, found that Paxlovid reduced the risk of COVID-19-related hospital admission. Compared with a placebo group, Paxlovid reduced the all-cause mortality rate by 89% within the three days of symptom onset. In June 2022, Clinical Infectious Diseases published the report of extensive research conducted to determine the effectiveness of Paxlovid in reducing severe COVID-19 and mortality in high-risk patients. Using a participant pool of 180,351 patients, the researchers demonstrated how Paxlovid significantly decreased the rate of severe COVID-19 and mortality. The drug also appears to be more effective in older and immunosuppressed patients. Paxlovid has since been granted emergency use authorization for the treatment of mild to moderate COVID-19 (Najjar-Debbiny et al., 2022).

Molnupiravir

Molnupiravir was initially developed as an antiviral medication indicated for influenza and Venezuelan equine encephalitic virus infections. Designed as an oral antiviral agent acting on the RdRp enzyme, the activity of Molnupiravir on SARS-CoV-2 was tested in multiple randomized trials. Results from the phase 2-3 studies of Molnupiravir found it to be effective in significantly reducing the rate of mortality and hospitalization in COVID-19 patients. Different double-blind, placebo-controlled randomized trials have reported that early treatment with Molnupiravir substantially improves the clinical outcome of mild to moderate COVID-19 while reducing the frequency of hospitalization and the risk of long-COVID complications (Jayk et al., 2022).

Although more antiviral drugs are repurposed for COVID-19 therapy, only a few have shown significant efficacy against SARS-CoV-2. Lopinavir/ Ritonavir is currently not indicated for COVID-19 therapy as data from randomized trials have reported no significant effects on clinical outcomes (Temsah et al., 2022). Hydroxychloroquine and chloroquine did not improve the overall mortality rate or prevent SARS-COV-2 infection (Avezum et al., 2022). Ivermectin is also not currently recommended in COVID-19 therapy as the proposed therapy regimen showed no significant resolution of symptoms (Rezai et al., 2022).

Immunomodulatory Agents

Tocilizumab

Tocilizumab, a humanized IgG1 monoclonal antibody, is commonly used to treat giant cell arteritis and juvenile arthritis. With its established effect on the interleukin-6 receptor, Tocilizumab is considered a suitable treatment in COVID-19 patients requiring mechanical ventilation and presenting with clinical signs suggesting raised inflammatory markers. It is recommended at a dose of 8 mg/kg and a maximum single dose limit of 800 mg. Administration of Tocilizumab should be done slowly over 1 hour in 100 mL of normal saline. Although there are conflicting thoughts on the efficacy of Tocilizumab in COVID-19 therapy, recent research reports showed that Tocilizumab effect a significant reduction in the mortality rate of COVID patients exhibiting rapid respiratory decompensation. It has also shown promising results in reducing the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia (Fernandez-Ruiz et al., 2022).

Corticosteroids

Cytokine release characterized by a raised volume of inflammatory markers has been linked with inflammatory-related lung injuries in SARS-COV-2 infection. There is a logical explanation for using corticosteroids as supportive therapy options during the early stages of the pandemic. Until recently, the efficacy of these medications in COVID-19 patients was poorly investigated. Recently, the result of the Randomized Evaluation of Covid-19 Therapy (RECOVERY) trial provided scientific backing for the use of corticosteroids, including dexamethasone (Luzzati et al., 2022).

This trial demonstrated how dexamethasone lowest the 28-day mortality rate of COVID-19 patients on invasive mechanical ventilation. Dexamethasone is recommended for hospitalized patients requiring noninvasive or invasive mechanical ventilation. According to updated CDC recommendations, dexamethasone should be administered orally once daily at a dose of 6 mg. Other recommended corticosteroids include prednisone (40 mg), methylprednisolone (32 mg), and hydrocortisone (160 mg).

Anti-SARS-CoV-2 Neutralizing Antibody Products

Convalescent Plasma Therapy

Convalescent plasma therapy was proposed based on clinical observations that effectively neutralized the SARS-CoV-2 virus (Cascella et al., 2022). This observation has led to the use of convalescent plasma therapy in patients showing no significant clinical response to first-line treatments. With this therapy option, plasma from recovered patients is injected into people yet infected or at the mild stage of infection. The therapeutic effects of convalescent plasma are linked to its neutralizing antibodies (Nabs), autoantibodies, and immune-modulatory cytokines. Antibodies in the plasma bind to the active SARS-CoV-2 virus, neutralizing its pathogenic effect by leveraging different biological pathways.

The antibody-virus interaction may include phagocytosis, antibody-dependent cellular cytotoxicity, and complement activation. Convalescent plasma also provides additional benefits to the recipients, including immunomodulation (Moura et al., 2022). Other anti-SARS-CoV-2 neutralizing antibody products under review include REGN-COV2 (Casirivimab and Imdevimab), Bamlanivimab, and Etesevimab (LY-CoV555 or LY3819253 and LY-CoV016 or LY3832479), Sotrovimab (VIR-7831), and REGN-COV2 (casirivimab and imdevimab).

Janus Kinase (JAK) Inhibitors

Baricitinib

In a July 29, 2021, announcement, the FDA cleared Baricitinib on an emergency authorization to treat COVID-19 in patients requiring supplemental oxygen. Baricitinib suppresses the KAK-STAT pathway, preventing the release of pro-inflammatory cytokines and systemic inflammation. Based on its complex interactions with the JAK and the AP2-associated protein kinase 1 (AAK1), Baricitinib is proposed to have anti-inflammatory and antiviral properties useful in COVID-19 patients (Akbarzadeh-Khiavi et al., 2022). Multiple randomized clinical trials investigating the antiviral properties of Baricitinib have found a significant clinical improvement in hospitalized COVID-19 patients. There are also reports of how Baricitinib reduces the 2-week mortality rate and accelerate clinical improvement in patients receiving oxygen supplementation or noninvasive ventilation (Huang et al., 2022). Other JAK inhibitors currently under review include Tofacitinib and Ruxolitinib.

SARS-CoV-2 Variants

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.

Alpha (B.1.1.7)

The Alpha variant was first identified and reported in September 2020 in the United Kingdom, becoming the dominant strain by the end of January 2021. By the end of December 2020, the alpha variant surpassed pre-existing variants to emerge as the predominant variant in the United States. This variant feature 17 different mutations in its genomes, with eight of these mutations appearing in the spike protein. The spike protein mutation increases the affinity of the virus to ACE2 receptors, enhancing attachment to the host cell and facilitating quick entry. Since it was first identified, different researchers have been designed to investigate the clinical implications of the Alpha variant. Extensive matched cohort studies have reported an increased mortality hazard ratio in patients infected with the alpha variant compared with other circulating variants (Saberiyan et al., 2022). The risk of death was more significant, and the outcome of complications in older patients also appeared to be substantial (Martin-Blondel et al., 2022). Several mutations in this variant also reduce the neutralizing capabilities of monoclonal antibody-based therapies (Sun et al., 2022).

Beta (B.1.351 lineage)

The Beta variant was first identified in May 2020 in South Africa, becoming the dominant variant in the African country in a short time. Unlike the alpha variant, this variant featured nine mutations on the spike protein, with three special mutations increasing its affinity for the ACE receptors in humans. By January 2021, the beta variants had emerged in the United States. The multiple spike mutations of the beta variant primarily caused the second wave of COVID-19 infections in South Africa and rapidly increased the number of infections recorded. Mathematical models estimated that the beta variant was 50% more transmissible than other pre-existing variants in South Africa (Madhi et al., 2022). The implications of the beta variant on therapy include an increased risk of transmission, reduction of monoclonal antibody therapy effect, and reduced post-vaccination sera.

Gamma (P.1 lineage)

First identified and reported in December 2020 in Brazil, the gamma variant was similar to the beta variant in a few mutation points. The identification of this variant provides a logical explanation for the abrupt increase in the number of COVID-19 hospitalizations and deaths in Brazil during this period. As with others, the gamma variants have ten different mutations on the spike protein. These mutations directly affect host cell attachment and entry. Mutation points also significantly reduce its susceptibility to monoclonal antibody treatments and allow it to resist neutralization by antibodies from convalescent plasma of recovered COVID-19 patients infected with earlier strains (Nicolete et al., 2022).

Delta (B.1.617.2 lineage)

The Delta variant was first identified in India in December 2020. It emerged as the dominant SARS-CoV-2 strain following the deadly wave of COVID-19 infections and death in the country in April 2021. Currently, the Delta variant is considered the dominant variant in the United States after it was first detected in March 2021. Like the Gamma variant, the Delta variant also featured different mutations on the spike protein. Preliminary investigations revealed that the Delta variant has a shorter incubation period in infected subjects. By June 2021, the Delta variant had replaced the Alpha variant as the dominant SARS-CoV-2 strain in the United Kingdom. Multiple clinical reviews have found that patients infected with the delta variants have a higher odd of requiring oxygen and intensive care admission. The mortality rate was significantly higher in many cases than in the ancestral strain. Compared with other strains, the severity of the symptoms was also higher in patients infected with this variant (Yazdanpanah et al., 2022).

Omicron (B.1.1.529 lineage)

First detected and identified in South Africa on 23 November 2021, the omicron variant is the most recently named variant as a VOC by the WHO. Omicron featured a different mutation behavior by exhibiting more than 30 unique mutations on the spike proteins. Mathematical modeling studies reported a 13-fold increase in viral infectivity, making it about 2.8 times more infective than the delta variant (Moshin et al., 2022). Omicron has demonstrated significant resistance against authorized monoclonal antibodies except for Sotrovimab (Planas et al., 2022).

SARS COV-2 Variants of Interest (VOIs)

In addition to alpha and other variants of concern (VOC), 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).

Healthcare Facilities and Public Health Recommendations on Prevention and Transmission

Universal Use of Face Masks

Primary transmission of the SARS-CoV-2 virus is through physical exposure to viral-laden droplets from infection individual. The correct and consistent use of face masks is recommended public health strategy for the prevention of transmission. With a large population of asymptomatic patients in high-risk locations, the general public is advised to use face masks when in transit or poor ventilated areas. Available evidence supports the use of cloth face masks for source control. In nursing homes and public health facilities for COVID-19 support and treatment, the updated CDC guideline recommends using non-valved, multilayered cloth masks. Health workers can also consider the use of N95 respirators if available. Non-disposable masks are recommended for community settings.

Limiting Contacts and Implementing Physical Distancing

Closed physical contact in crowded spaces has been linked with an increased transmission rate. Since the virus can be transmitted through viral respiratory droplets suspended in the air, implementing a physical distancing policy in high-burden communities has been recommended. The current guideline recommends maintaining a physical distance of at least 6 feet from suspected active infection cases and asymptomatic individuals. In many epidemiological surveys, the highest transmission rates have been documented in high-density areas and household settings (McLean et al., 2022). Setting a physical barrier and promoting visual reminders might help reduce the rate of new infections.

Increased Testing, Diagnosis, and Isolation

Although minor differences in percentages are reported, about 40% of all active COVID-19 cases are reportedly asymptomatic. Consequently, the transmission from presymptomatic and asymptomatic patients accounts for about 50% of all transmission cases (Luo et al., 2022). Increased testing for new cases is considered the best strategy for identifying the transmission trend and reducing the risk of silent transmission in a population. Routine testing in persons with known exposure is recommended. Routine testing can be planned based on occupational or residential settings and should be increased in communities with an upward trend in transmission rates. In addition, prompt isolation of all confirmed diagnoses of COVID-19 infection should be encouraged.

Contact tracing, Quarantining, and Close Contact Testing

Every confirmed diagnosis should be followed up with a thorough case investigation. This process includes obtaining detailed information about possible transmission modes, identifying and communicating with people exposed to the active case, and collating relevant healthcare information. Contact exposed to the active case should be educated on the risk of exposure, symptoms of the disease, and why they should undergo testing. Quarantining should follow all contact tracing procedures and involves isolating all exposed contacts and implementing a close observations schedule to check for symptom developments.

Other preventions strategies recommended by the CDC include:

  • Avoiding nonessential indoor and outdoor gatherings
  • Safeguarding people and special populations at risk of severe illness or death
  • Protecting essential workers
  • Avoiding traveling to high-risk locations
  • Improving room ventilation
  • Enhancing personal hygiene, space cleaning, and disinfection
  • Vaccination

Vaccines and Vaccination Strategies

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 have 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 et al., 2022).

As of June 30, 2022, the CDC guideline on vaccines and vaccination strategies only recognizes three COVID-19 vaccines approved by the FDA under the Emergency Use Authorization (EUA) and the Biologics License Application (BLA) schedules. These vaccines include:

Pfizer-BioNTech COVID-19 Vaccine/COMIRNATY
 Primary SeriesBooster doses
Age IndicationVaccine vial cap colorLabel border colorDilution requiredDoseInjection volumeDoseInjection volume
6 months-4 yearsMaroonMaroonYes3 µg0.2 mLNANA
5-11 yearsOrangeOrangeYes10 µg0.2 mL10 µg0.2 mL
12 years and olderPurplePurpleYes30 µg0.3 mL30 µg0.3 mL
12 years and olderGrayGrayNo30 µg0.3 mL30 µg0.3 mL

Fig.4: Source; Vaccines and Immunizations, CDC. Update: July 20, 2022. Available here.

Moderna COVID-19 Vaccine/SPIKEVAX
 Primary SeriesBooster doses
Age IndicationVaccine vial cap colorLabel border colorDilution requiredDoseInjection volumeDoseInjection volume
6 months-5 yearsDark blueMagentaNo25 µg0.25 mLNANA
6-11 yearsDark bluePurpleNo50 µg0.5 mLNANA
12-17 yearsRedLight blueNo100 µg0.5 mLNANA
18 years and olderRedLight blueNo100 µg0.5 mL50 µg0.25 mL
18 years and olderDark bluePurpleNoNANA50 µg2.5 mL

Fig.5: Source; Vaccines and Immunizations, CDC. Update: July 20, 2022. Available here.

Janssen (Johnson & Johnson) COVID-19 Vaccine
 Primary SeriesBooster doses
Age IndicationVaccine vial cap colorLabel border colorDilution requiredDoseInjection volumeDoseInjection volume
18 years and olderBlueNo ColorNo5x1010 viral particles0.5 mL5x1010 viral particles0.5 mL

Fig.6: Source; Vaccines and Immunizations, CDC. Update: July 20, 2022. Available here.

Novavax
 Primary SeriesBooster doses
Age IndicationVaccine vial cap colorLabel border colorDilution requiredDoseInjection volumeDoseInjection volume
18 years and olderRoyal BlueNo ColorNo5 µg rS and 50 µg of Matrix-M™ adjuvant0.5 mLNANA

Fig. 7: Source; Vaccines and Immunizations, CDC. Update: July 20, 2022. Available here.

The current CDC guideline also recommends an mRNA vaccine (Pfizer or Moderna) for primary and booster vaccination in all populations. On the other hand, the Janssen vaccine is recommended for adults aged 18 and above, with a strict warning on the possible risk of thrombosis and thrombocytopenia syndrome. 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 recipients' age and the day of vaccination.

COVID-19 Vaccination Schedule for People who ARE moderately or severly immunocompromised chart

Fig.6; Vaccines and Immunizations, CDC. Updated; June 30, 2022. Available here.

COVID-19 Vaccination Schedule for People who are NOT moderately or severely immunocompromised Chart

Fig.7; Vaccines and Immunizations, CDC. Updated; June 30, 2022. Available here.

In October 2022, the Florida Department of Health issued guidance for mRNA COVID-19 vaccines for adult and pediatric patients. These guidances can be found at Guidance for mRNA COVID-19 Vaccines and Guidance for Pediatric COVID-19 Vaccines.

Special Population Considerations

Infants and Young Children

According to the CDC, as of June 2022, there is currently no FDA-approved or FDA-authorized COVID-19 vaccination available for children younger than six months of age.

Pre-term infants (those born before 37 weeks' gestation), regardless of their weight at birth, are eligible to receive COVID-19 vaccination at their chronological age and abide by the same schedule that full-term infants and children utilize (CDC, 2022).

Children Who Transition from A Younger to An Older Age Group During Vaccine Series

Another common question is what dose should be given to a child who transitions to an older age group within their COVID-19 vaccine course series. The CDC recommends that all vaccine recipients receive the age-appropriate dosage that is recommended for their age and day of vaccination (CDC, 2022). See the following examples below for guidance based on the respective vaccine products (CDC, 2022):

  • Pfizer-BioNTech COVID-19 Vaccine/COMIRNATY:
    • For a child who started a primary series at age 4, their dose is 0.20 mL (3 mcg) of the maroon cap/maroon label border Pfizer-BioNTech vaccine that is authorized for children ages 6 months to 4 years.
    • In the 3-8 week span before their second dose, the child turns 5.
    • Now that the child is 5, they move into the next higher age/dosage group.
    • Their second dose of the series will now be 0.20 mL (10 mcg) of the orange cap/orange label border Pfizer-BioNTech vaccine authorized for children ages 5-11.
    • The child will then wait the following 8 weeks before dose #3.
    • The child's third and final dose of the series will then again be 0.20 mL (10 mcg) of the orange cap/orange label border Pfizer-BioNTech vaccine authorized for children ages 5-11.

For additional examples and visuals, visit the CDC's Pfizer-BioNTech COVID-19 vaccine PDF here.

  • Moderna COVID-19 Vaccine/SPIKEVAX:
    • For a child who started a primary series at age 5, their dose is 0.25 mL (25 mcg) of the dark blue cap/magenta label border Moderna vaccine that is authorized for children ages 6 months to 5 years.
    • In the 4-8 week span before their second dose, the child turns 6.
    • Now that the child is 6, they move into the next higher age/dosage group.
    • Their second and final dose of the series will now be 0.50 mL (50 mcg) of the dark blue cap/purple label border Moderna vaccine authorized for children ages 6-11.

For additional examples and visuals, visit the CDC's Moderna COVID-19 vaccine PDF here.

Pregnant Individuals

The safety and efficacy of COVID-19 vaccination during pregnancy contribute to the benefits outweighing any potential risks of vaccination (CDC, 2022). Because pregnancies affected by COVID-19 are associated with an increased risk of stillbirths or pre-term birth, it is recommended by the CDC that pregnant individuals receive COVID-19 vaccination and ensure to stay up to date with CDC recommendations regarding further updates and/or boosters (CDC, 2022). Recent studies have revealed that the antibodies produced in the pregnant individual following vaccination are transferred to the newborn, reducing the risk of COVID-19 hospitalization in children less than 6 months of age (CDC, 2022).

Lactating Individuals

Because COVID-19 vaccination clinical trials did not include lactating individuals, there is limited data on the effects of COVID-19 vaccines on breastfed infants and milk production (CDC, 2022). Recent studies have shown that antibodies developed from vaccination during or even after pregnancy are found in breast milk samples (CDC, 2022). Again, given the benefits versus the risks, the CDC does recommend COVID-19 vaccination for all lactating individuals (CDC, 2022).

Long-Term Complications in COVID-19 Patients

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 reveal 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 bout lasting for about 8 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.

Conclusion

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. Clinical is 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 the viral disease goes a long way in eliminating the virus and maintaining a healthy global population.

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Implicit Bias Statement

CEUFast, Inc. is committed to furthering diversity, equity, and inclusion (DEI). While reflecting on this course content, CEUFast, Inc. would like you to consider your individual perspective and question your own biases. Remember, implicit bias is a form of bias that impacts our practice as healthcare professionals. Implicit bias occurs when we have automatic prejudices, judgments, and/or a general attitude towards a person or a group of people based on associated stereotypes we have formed over time. These automatic thoughts occur without our conscious knowledge and without our intentional desire to discriminate. The concern with implicit bias is that this can impact our actions and decisions with our workplace leadership, colleagues, and even our patients. While it is our universal goal to treat everyone equally, our implicit biases can influence our interactions, assessments, communication, prioritization, and decision-making concerning patients, which can ultimately adversely impact health outcomes. It is important to keep this in mind in order to intentionally work to self-identify our own risk areas where our implicit biases might influence our behaviors. Together, we can cease perpetuating stereotypes and remind each other to remain mindful to help avoid reacting according to biases that are contrary to our conscious beliefs and values.

References

  • Abdullaev, A., Abdurakhimov, A., Mirakbarova, Z., Ibragimova, S., Tsoy, V., Nuriddinov, S., Dalimova, D., Turdikulova, S., & Abdurakhmonov, I. (2022). Genome sequence diversity of SARS-CoV-2 was obtained from clinical samples in Uzbekistan. PloS one, 17(6), e0270314. Visit Source.
  • Akbarzadeh-Khiavi M, Torabi M, Rahbarnia L, Safary A. Baricitinib combination therapy: a narrative review of repurposed Janus kinase inhibitor against severe SARS-CoV-2 infection. Infection. 2022 Apr;50(2):295-308. Visit Source.
  • Alafif, T., Etaiwi, A., Hawsawi, Y., Alrefaei, A., Albassam, A., & Althobaiti, H. (2022). DISCOVID: discovering patterns of COVID-19 infection from recovered patients: a case study in Saudi Arabia. International Journal of Information Technology, 1–14. Advance online publication. Visit Source.
  • Al-Saadi EAKD, Abdulnabi MA. Hematological changes associated with COVID-19 infection. J Clin Lab Anal. 2022 Jan;36(1): e24064. doi: 10.1002/jcla.24064. Epub 2021 Nov 16. Visit Source.
  • Avezum Á, Oliveira GBF, Oliveira H, Lucchetta RC, Pereira VFA, Dabarian AL, D O Vieira R, Silva DV, Kormann APM, Tognon AP, De Gasperi R, Hernandes ME, Feitosa ADM, Piscopo A, Souza AS, Miguel CH, Nogueira VO, Minelli C, Magalhães CC, Morejon KML, Bicudo LS, Souza GEC, Gomes MAM, Fo JJFR, Schwarzbold AV, Zilli A, Amazonas RB, Moreira FR, Alves LBO, Assis SRL, Neves PDMM, Matuoka JY, Boszczowski I, Catarino DGM, Veiga VC, Azevedo LCP, Rosa RG, Lopes RD, Cavalcanti AB, Berwanger O; COPE - COALITION COVID-19 Brazil V Investigators. Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE - Coalition V): A double-blind, multicentre, randomised, controlled trial. Lancet Reg Health Am. 2022 Jul; 11:100243. Visit Source.
  • Basu-Ray I, Almaddah NK, Adeboye A, Soos MP. Cardiac Manifestations of Coronavirus (COVID-19). 2022 May 2. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. Visit Source.
  • Blanco, N. C., Quintana, J., Mendoza, M., Botero, C., Rodríguez, L. C., Villa, S. C., Mazuera, A., Díaz, J., García, B. U., Riveros, C., & Alban, J. (2022). Guillain-Barré syndrome associated with SARS-CoV-2 infection: A case series from 4 Colombian cities during the pandemic [Síndrome de Guillain Barré y Sars Cov2: serie de casos en el primer año de pandemia]. Neurology Perspectives, Advance online publication. Visit Source.
  • Borch L, Holm M, Knudsen M, Ellermann-Eriksen S, Hagstrom S. Long COVID symptoms and duration in SARS-CoV-2 positive children - a nationwide cohort study. Eur J Pediatr. 2022 Apr;181(4):1597-1607. Visit Source.
  • Cascella M, Rajnik M, Aleem A, et al. Features, Evaluation, and Treatment of Coronavirus (COVID-19) [Updated 2022 May 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Visit Source.
  • Chakrabartty, I., Khan, M., Mahanta, S., Chopra, H., Dhawan, M., Choudhary, O. P., Bibi, S., Mohanta, Y. K., & Emran, T. B. (2022). Comparative overview of emerging RNA viruses: Epidemiology, pathogenesis, diagnosis and current treatment. Annals of medicine and surgery (2012), 79, 103985. Visit Source.
  • Chuang HN, Shih CH, Tsai HW, Jiang RS, Hsiao TH, Liu PY, Jan YJ, Wang JM. Laboratory Surge Response to the COVID-19 Pandemic: An Incident Command System Approach. J Multidiscip Healthc. 2022 May 11; 15:1083-1088. Visit Source.
  • D'Ardes D, Tana C, Salzmann A, Ricci F, Guagnano MT, Giamberardino MA, Cipollone F. Ultrasound assessment of SARS-CoV-2 pneumonia: a literature review for the primary care physician. Ann Med. 2022 Dec;54(1):1140-1149. Visit Source.
  • Dhar, B.C. Diagnostic assay and technology advancement for detecting SARS-CoV-2 infections causing the COVID-19 pandemic. Anal Bioanal Chem 414, 2903–2934 (2022). Visit Source.
  • Temsah MH, Al-Jelaify M, Memish ZA. Guidance for the pharmacological management of COVID-19 in the emergency setting. Expert Opin Pharmacother. 2022 Apr;23(6):639-642. Visit Source.
  • Enabulele O, MoBellaji A. COVID-19 pandemic: an assessment of risk perception and the implementation of precautionary measures in a group of primary care workers in Nigeria. J Prev Med Hyg. 2022 Jan 31;62(4). Visit Source.
  • Fernández-Ruiz M, López-Medrano F, Carretero O, Parra P, Ruiz-Merlo T, Aguado JM; H12O Immunomodulation Therapy for COVID-19 Group. Tocilizumab therapy in SARS-CoV-2 pneumonia: A matched retrospective cohort analysis. Med Clin (Engl Ed). 2022 Jun 24;158(12):608-612. Visit Source.
  • Gao, X., Zhang, S., Gou, J., Wen, Y., Fan, L., Zhou, J., Zhou, G., Xu, G., & Zhang, Z. (2022). Spike-mediated ACE2 down-regulation is involved in the pathogenesis of SARS-CoV-2 infection. The Journal of Infection, Advance online publication. Visit Source.
  • Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, Oguchi G, Ryan P, Nielsen BU, Brown M, Hidalgo A, Sachdeva Y, Mittal S, Osiyemi O, Skarbinski J, Juneja K, Hyland RH, Osinusi A, Chen S, Camus G, Abdelghany M, Davies S, Behenna-Renton N, Duff F, Marty FM, Katz MJ, Ginde AA, Brown SM, Schiffer JT, Hill JA; GS-US-540-9012 (PINETREE) Investigators. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Engl J Med. 2022 Jan 27;386(4):305-315. Visit Source.
  • Huang, J., Zhou, C., Deng, J., & Zhou, J. (2022). JAK Inhibition as a New Treatment Strategy for Patients with COVID-19. Biochemical pharmacology, 202, 115162. Advance online publication. Visit Source.
  • Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, Martín-Quirós A, Caraco Y, Williams-Diaz A, Brown ML, Du J, Pedley A, Assad C, Strizki J, Grobler JA, Shamsuddin HH, Tipping R, Wan H, Paschke A, Butterton JR, Johnson MG, De Anda C; MOVe-OUT Study Group. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022 Feb 10;386(6):509-520. Visit Source.
  • Jdiaa, S.S., Mansour, R., El Alayli, A. et al. COVID–19 and chronic kidney disease: an updated overview of reviews. J Nephrol 35, 69–85 (2022). Visit Source.
  • Jeganathan K, Paul ABM. Vertical transmission of SARS-CoV-2: A systematic review. Obstet Med. 2022 Jun;15(2):91–8. Visit Source.
  • Katsoularis I, Fonseca-Rodríguez O, Farrington P, Jerndal H, Lundevaller EH, Sund M, Lindmark K, Fors Connolly AM. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study. BMJ. 2022 Apr 6;377: e069590. Visit Source.
  • Kirtipal N, Kumar S, Dubey SK, Dwivedi VD, Gireesh Babu K, Malý P, Bharadwaj S. Understanding of the possible routes for SARS CoV-2 invasion via ACE2 in the host linked with multiple organs damage. Infect Genet Evol. 2022 Apr; 99:105254. Visit Source.
  • Kurver L, van den Kieboom CH, Lanke K, Diavatopoulos DA, Overheul GJ, Netea MG, Ten Oever J, van Crevel R, Mulders-Manders K, van de Veerdonk FL, Wertheim H, Schouten J, Rahamat-Langendoen J, van Rij RP, Bousema T, van Laarhoven A, de Jonge MI. SARS-CoV-2 RNA in exhaled air of hospitalized COVID-19 patients. Sci Rep. 2022 May 30;12(1):8991. Visit Source.
  • Latifi-Pupovci H. (2022). Molecular mechanisms involved in the pathogenicity of SARS-CoV-2: Immune evasion and implications for therapeutic strategies. Biomedicine & Pharmacotherapy, 153, 113368. Visit Source.
  • Leng, T., Hill, E. M., Keeling, M. J., Tildesley, M. J., & Thompson, R. N. (2022). The effect of notification window length on the epidemiological impact of COVID-19 contact tracing mobile applications. Communications medicine, 2, 74. Visit Source.
  • Li, J., Jia, H., Tian, M., Wu, N., Yang, X., Qi, J., Ren, W., Li, F., & Bian, H. (2022). SARS-CoV-2 and Emerging Variants: Unmasking Structure, Function, Infection, and Immune Escape Mechanisms. Frontiers in cellular and infection microbiology, 12, 869832. Visit Source.
  • Luo T, Cao Z, Wang Y, Zeng D, Zhang Q. Role of Asymptomatic COVID-19 Cases in Viral Transmission: Findings from a Hierarchical Community Contact Network Model. IEEE Trans Autom Sci Eng. 2021 Sep 3;19(2):576-585. Visit Source.
  • Luzzati, R., De Luca, M., Sanson, G., Borelli, M., Biolo, G., Giacomazzi, D., Zerbato, V., & Di Bella, S. (2022). The potential of outpatient steroid therapy in elderly patients with early COVID-19. Aging clinical and experimental research, 1–6. Advance online publication. Visit Source.
  • Madhi SA, Kwatra G, Myers JE, Jassat W, Dhar N, Mukendi CK, Nana AJ, Blumberg L, Welch R, Ngorima-Mabhena N, Mutevedzi PC. Population Immunity and Covid-19 Severity with Omicron Variant in South Africa. N Engl J Med. 2022 Apr 7;386(14):1314-1326. Visit Source.
  • Martin-Blondel G, Lescure FX, Assoumou L, Charpentier C, Chapplain JM, Perpoint T, Grouteau G, Cordel H, Pialoux G, Pacanowski J, Thy M, Bauvois A, Laureillard D, Hamrouni F, Algarte-Genin M, Poissy J, Descamps D, Costagliola D; CoCliCo Study Group. Increased risk of severe COVID-19 in hospitalized patients with SARS-CoV-2 Alpha variant infection: a multicentre matched cohort study. BMC Infect Dis. 2022 Jun 13;22(1):540. Visit Source.
  • McLean HQ, Grijalva CG, Hanson KE, Zhu Y, Deyoe JE, Meece JK, Halasa NB, Chappell JD, Mellis AM, Reed C, Belongia EA, Talbot HK, Rolfes MA. Household Transmission and Clinical Features of SARS-CoV-2 Infections. Pediatrics. 2022 Mar 1;149(3): e2021054178. Visit Source.
  • Mohsin M, Mahmud S. Omicron SARS-CoV-2 variant of concern: A review on its transmissibility, immune evasion, reinfection, and severity. Medicine (Baltimore). 2022 May 13;101(19): e29165. Visit Source.
  • Moodley S, Sewchuran T. Chest radiography evaluation in patients admitted with confirmed COVID-19 infection, in a resource-limited South African isolation hospital. SA J Radiol. 2022 Jan 17;26(1):2262. Visit Source.
  • Moura LW, Liao AW, Negrini R, Zlotnik E. The use of convalescent plasma therapy in the management of a pregnant woman with COVID-19: a case report. Einstein (Sao Paulo). 2022 Feb 16;20: eRC6550. Visit Source.
  • Najjar-Debbiny R, Gronich N, Weber G, Khoury J, Amar M, Stein N, Goldstein LH, Saliba W. Effectiveness of Paxlovid in Reducing Severe COVID-19 and Mortality in High-Risk Patients. Clin Infect Dis. 2022 Jun 2: Visit Source.
  • Nicolete VC, Rodrigues PT, Fernandes ARJ, Corder RM, Tonini J, Buss LF, Sales FC, Faria NR, Sabino EC, Castro MC, Ferreira MU. Epidemiology of COVID-19 after Emergence of SARS-CoV-2 Gamma Variant, Brazilian Amazon, 2020-2021. Emerg Infect Dis. 2022 Mar;28(3):709-712. Visit Source.
  • Niknam, Z., Jafari, A., Golchin, A. et al. Potential therapeutic options for COVID-19: an update on current evidence. Eur J Med Res 27, 6 (2022). Visit Source.
  • Odada, D. E., Ndai, J., Kimeu, J., Shah, J., & Shah, R. (2022). Preadmission Testing for COVID-19 as a Screening Strategy: A Retrospective Chart Review from a Tertiary Hospital in Kenya. Infection Prevention in Practice, 100231. Advance online publication. Visit Source.
  • Ortega, M. A., García-Montero, C., Fraile-Martinez, O., Colet, P., Baizhaxynova, A., Mukhtarova, K., Alvarez-Mon, M., Kanatova, K., Asúnsolo, A., & Sarría-Santamera, A. (2022). Recapping the Features of SARS-CoV-2 and Its Main Variants: Status and Future Paths. Journal of personalized medicine, 12(6), 995. Visit Source.
  • Panagouli ED, Thirios AC, Psaltopoulou T, Bacopoulou F, Troupis TG, Chrousos GP, Tsolia MN, Sergentanis TN, Tsitsika AK. COVID-19 features in children and adolescents: a systematic review and pooled analysis. EMBnet J. 2021 Jul;26:e946. Visit Source.
  • Paoletti, A. M., Melilli, M. G., & Vecchio, I. (2022). Experimental Models of SARS-COV-2 Infection in the Central Nervous System. Journal of central nervous system disease, 14, 11795735221102231. Visit Source.
  • Park JH, Cha MJ, Choi H, Kim MC, Chung JW, Lee KS, Jeong DG, Baek MS, Kim WY, Lim Y, Yoon SW, Choi SH. Relationship between SARS-CoV-2 antibody titer and the severity of COVID-19. J Microbiol Immunol Infect. 2022 May 5:S1684-1182(22)00059-7. Visit Source.
  • Planas D, Saunders N, Maes P, Guivel-Benhassine F, Planchais C, Buchrieser J, Bolland WH, Porrot F, Staropoli I, Lemoine F, Péré H, Veyer D, Puech J, Rodary J, Baele G, Dellicour S, Raymenants J, Gorissen S, Geenen C, Vanmechelen B, Wawina-Bokalanga T, Martí-Carreras J, Cuypers L, Sève A, Hocqueloux L, Prazuck T, Rey FA, Simon-Loriere E, Bruel T, Mouquet H, André E, Schwartz O. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature. 2022 Feb;602(7898):671-675. Visit Source.
  • Rezai MS, Ahangarkani F, Hill A, Ellis L, Mirchandani M, Davoudi A, Eslami G, Roozbeh F, Babamahmoodi F, Rouhani N, Alikhani A, Najafi N, Ghasemian R, Mehravaran H, Hajialibeig A, Navaeifar MR, Shahbaznejad L, Rahimzadeh G, Saeedi M, Alizadeh-Navai R, Moosazadeh M, Saeedi S, Razavi-Amoli SK, Rezai S, Rostami-Maskopaee F, Hosseinzadeh F, Movahedi FS, Markowitz JS, Valadan R. Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19; Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials. Front Med (Lausanne). 2022 Jun 16;9:919708. 
  • Sabaghian T, Kharazmi AB, Ansari A, Omidi F, Kazemi SN, Hajikhani B, Vaziri-Harami R, Tajbakhsh A, Omidi S, Haddadi S, Shahidi Bonjar AH, Nasiri MJ, Mirsaeidi M. COVID-19, and Acute Kidney Injury: A Systematic Review. Front Med (Lausanne). 2022 Apr 4; 9:705908. Visit Source.
  • Saberiyan M, Karimi E, Khademi Z, Movahhed P, Safi A, Mehri-Ghahfarrokhi A. SARS-CoV-2: phenotype, genotype, and characterization of different variants. Cell Mol Biol Lett. 2022 Jun 17;27(1):50. Visit Source.
  • Sen A, Nigam A, Vachher M. Role of Polypeptide Inflammatory Biomarkers in the Diagnosis and Monitoring of COVID-19. Int J Pept Res Ther. 2022;28(2):59. Visit Source.
  • Sobolewska-Pilarczyk M, Pokorska-Śpiewak M, Stachowiak A, Marczyńska M, Talarek E, Ołdakowska A, Kucharek I, Sybilski A, Mania A, Figlerowicz M, Mazur-Melewska K, Potocka P, Sulik A, Hasiec B, Stani M, Frańczak-Chmura P, Szczepańska B, Pałyga-Bysiecka I, Ciechanowski P, Łasecka-Zadrożna J, Zaleska I, Szenborn L, Dryja U, Kuchar E, Niedźwiecka S, Kalicki B, Flisiak R, Pawłowska M. COVID-19 infections in infants. Sci Rep. 2022 May 11;12(1):7765. Visit Source.
  • Sodeifian F, Mushtaq S, Rezaei N. Cutaneous manifestation of COVID-19: What have we learned a year into the pandemic? Actas Dermosifiliogr. 2022 Feb;113(2):157-165. Visit Source.
  • Sun C, Xie C, Bu GL, Zhong LY, Zeng MS. Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants. Signal Transduct Target Ther. 2022 Jun 28;7(1):202. Visit Source.
  • Sun, C., Xie, C., Bu, G. L., Zhong, L. Y., & Zeng, M. S. (2022). Molecular characteristics, immune evasion, and impact of SARS-CoV-2 variants. Signal transduction and targeted therapy, 7(1), 202. Visit Source.
  • Sussman RA, Golberstein E, Polosa R. Analytic modeling and risk assessment of aerial transmission of SARS-CoV-2 virus through vaping expirations in shared micro-environments. Environ Sci Pollut Res Int. 2022 Jun 27:1–25. 
  • Tomasino B, Pellitteri G, Bax F, Marini A, Surcinelli A, Gigli GL, Valente M. Multisensory mental representation in covid-19 patients and the possibility of long-lasting gustatory and olfactory dysfunction in the CNS. Sci Rep. 2022 May 5;12(1):7340. Visit Source.
  • Unione, L., Moure, M. J., Lenza, M. P., Oyenarte, I., Ereño-Orbea, J., Ardá, A., & Jiménez-Barbero, J. (2022). The SARS-CoV-2 Spike Glycoprotein Directly Binds Exogeneous Sialic Acids: A NMR View. Angewandte Chemie(International ed. in English), 61(18), e202201432. Visit Source.
  • Upreti S, Samant M. A Review on Immunological Responses to SARS-CoV-2 and Various COVID-19 Vaccine Regimens. Pharm Res. 2022 Jul 1:1–16. Visit Source.
  • Valderas C, Méndez G, Echeverría A, Suarez N, Julio K, Sandoval F. COVID-19 and neurologic manifestations: a synthesis from the child neurologist's corner. World J Pediatr. 2022 Jun;18(6):373-382. Visit Source.
  • Wang J, Dong W. COVID-19: the possibility, ways, mechanisms, and interruptions of mother-to-child transmission. Arch Gynecol Obstet. 2022 Jun 4:1–10. Visit Source.
  • Yan, W., Zheng, Y., Zeng, X. et al. Structural biology of SARS-CoV-2: open the door for novel therapies. Sig Transduct Target Ther 7, 26 (2022). Visit Source.
  • Yazdanpanah F, Yazdanpanah S, Rezaei N. COVID-19 Delta variation; more contagious or more pernicious? Acta Biomed. 2022 Jan 19;92(6): e2021454. Visit Source.
  • Zeng W, Qi K, Ye M, Zheng L, Liu X, Hu S, Zhang W, Tang W, Xu J, Yu D, Wei Y. Gastrointestinal symptoms are associated with severity of coronavirus disease 2019: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2022 Feb 1;34(2):168-176. Visit Source.
  • Zhao N, Zhou N, Fan H, Ding J, Xu X, Dong X, Dong X, Xu D, Min X, Yu Y, Gong H, Mao L, He M. Mutations and Phylogenetic Analyses of SARS-CoV-2 Among Imported COVID-19 From Abroad in Nanjing, China. Front Microbiol. 2022 Mar 17; 13:851323. Visit Source.