Updated date:

What Are the Current (Evidence-Based) Opportunities for the Clinical Management of COVID-19?

Dr. Khalid is a physician, a researcher, a health writer, and holds a Ph.D. in clinical research.

COVID-19 Structure

COVID-19 Structure

Background of COVID-19?

COVID-19, or SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), is a highly contagious virus with the potential to rapidly invade the human physiological system. The WHO (World Health Organization) declared COVID-19 as a PHEIC (public health emergency of international concern) on 3rd January 2020 in compliance with IHR (International Health Regulations) (Cascella, Rajnik, Cuomo, Dulebohn, & Napoli, 2020).

When It Began

26th February 2020 was the day when the 1st COVID-19 infection based on location transmission was tracked by the United States of America. The virus was initially recognized as 2019-nCoV; however, it was later renamed as SARS-CoV-2 by ICTV (International Committee on Taxonomy of Viruses).

What It Does

The virus primarily invades the human respiratory system and is reportedly found in various animal species. Clinicians recognize SARS-CoV-2 based on its relationship with +ssRNA (single-stranded RNA viruses) family. The virus has reportedly the potential to invade from animals to humans in a manner to cause respiratory system complications. The virus is known to cause clinical complications similar to SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) (Cascella et al., 2020). However, the common cold is the most commonly reported complication of the virus in otherwise healthy individuals. No confirmatory evidence is available so far concerning the origin of SARS-CoV-2; however, its animal origin is at large presumed and hypothesized by the scientific community. SARS-CoV-2 continues to increase serious public health risk while its local transmission has led to the global lockdown, thereby causing health and socioeconomic deterioration of masses to an unprecedented level.

Outlook of the Disease

WHO had alarmed the global community regarding the extreme health threat from the virus on 28th February 2020 (Cascella et al., 2020). COVID-19 was declared as a pandemic by WHO in March 2020 since the infection impacted more than 114 nations (outside China). WHO situation reports continue to display and emphasize the disastrous impact of COVID-19 transmission on the entire humanity. The consistently increasing number of infectious cases and death toll under the impact of COVID-19 transmission has forced the entire world to unanimously mitigate the adverse impact of the pandemic while configuring preventive and prophylactic interventions to challenge and contain local transmission of the virus across the human populations (Cascella et al., 2020).

Clinicians and scientists stand clueless regarding the peak-time of the pandemic along with its duration, mode of evolution and human-virus interaction paradigm. The shock wave arising from the COVID-19 pandemic has not only challenged the global health care systems but also forced the health care professionals to revisit each level of their disaster management systems.

Etiology of COVID-19

The electron microscopy has revealed the crown-like structure of the positive-stranded RNA virus (i.e. COVID-19) (Cascella et al., 2020). The crown-like appearance of this virus is based on its spike glycoproteins. This is why the scientists initially called it ‘coronam’. The classification of COVID-19 is mentioned below.

  1. Family: Coronaviridae
  2. Subfamily: Orthocoronavirinae
  3. Order: Nidovirales

Coronaviruses have the potential to cause a range of neurological, hepatic, enteric, and respiratory disease conditions (Cascella et al., 2020). They also can infect bats, cats, cattle, and camels. Indeed, seven types of coronaviruses can cause serious clinical complications inside their human hosts. Clinicians and researchers presume 2% healthy carriers of coronaviruses.

Furthermore, these viruses predominantly lead to acute respiratory infections or self-limiting acute respiratory complications in people with a strong immune system. They are known to cause lower respiratory tract infections in immunocompromised individuals (Cascella et al., 2020). SARS-COV-2 is known to cause extra-respiratory and respiratory complications in individuals of all age groups. The mortality rates reportedly vary between 10% to 35% irrespective of age.

SARS-CoV-2 exhibits pleomorphism and associated with the category of beta-CoVs. The elliptical or round structure of this virus has the potential to change its form to an unpredictable extent (Cascella et al., 2020). The 60-140nm diameter of this virus is specific to its complicated structure. The evidence-based research literature reveals the sensitivity of SARS-CoV-2 to heat and ultraviolet radiation. However, clinical literature does not unequivocally affirm the potential of UV light to deactivate the structure and function of the virus.

Coronaviruses also exhibit sensitivity to chloroform, peroxyacetic acid, chlorine-based disinfectants, ethanol, 75% ether, and other lipid solvents. The genetic configuration of SARS-CoV-2 exhibits 82%-89% similarity with human SARS-CoV and SARS-like CoVZXC21 (Cascella et al., 2020). The genetic structure of SARS-CoV-2 is based on 9860 amino acids and 29891 nucleotides arranged in a single-stranded RNA. Scientists presume the mutation capacity of SARS-CoV-2 in the context of producing an intermediary virulent strain of the pathogen in the human population.

Does SARS-CoV-2 Remain Structurally and Functionally Stable Under Variable Environmental Conditions?

SARS-CoV-2 strikingly survives on smooth structures for a long duration (Chin et al., 2020). The scientists do not rule out the possibility of the survival of SARS-Cov-2 on surgical masks for a duration of seven days or more. The non-infectious strain of this virus could be retrieved from otherwise healthy individuals who are found to be SARS-CoV-2 positive through RT-PCR analysis. The structural stability pattern of SARS-CoV-2 on smooth surfaces is still not completely known to the researchers. However, this could probably be the outcome of 12-point mutations and the conservative nature of SARS-CoV-2. Several mutations in the virus modify its receptor-binding properties while changing the structure and function of its hydrogen bonds (Tahirul-Qamar, Alqahtani, Alamri, & Chen, 2020).

What Are the Current Treatment Opportunities for SARS-CoV-2 Management?

Is There any Standard Pharmacotherapy or Alternative Treatment Approach for SARS-CoV-2 Management?

No standard therapeutic protocol has been so far developed by the scientific community for the treatment of SARS-CoV-2. The case fatality rate based on the SARS-CoV-2 pandemic is reportedly highest in individuals affected with multiple organ failure, septic shock, respiratory failure/chronic respiratory disease, cancer, hypertension, diabetes, and cardiovascular disease (Li, 2020). Clinicians need to devise treatments for such patients based on the clinical correlation of symptomatology and lab findings (Fisher & Heymann, 2020). Clinicians, health care practitioners, and rehabilitators also require considering the socioeconomic, environmental, and emotional impact of SARS-CoV-2 pandemic on the overall health and wellness of individuals and accordingly configure meaningful treatment strategies for remediation (Bandyopadhyay, 2020).

The treatment of SARS-CoV-2 patients’ physical symptoms and behavioral manifestations continue to challenge the health care systems across the globe to an unprecedented level. Most importantly, the treatment of stress, depression, and anxiety of healthy individuals based on global lockdown circumstances and resource mismanagement prove highly challenging for the health care professions (Wang et al., 2020). SARS-CoV-2 pandemic has forced the medical community to rethink and revisit the existing health care structures and disaster management strategies due to their incapacity to contain the disease.

Is There Any First-Line Therapy for COVID-19 Management?

SARS-CoV-2 manifests through the development of inflammatory lung infiltration, shortness of breath, coughing, and fever inside the human host (T, 2020). The first-line therapeutic management of SARS-CoV-2 infection is based on the stringent isolation of the affected/suspected patients followed by the close assessment of their oxygen saturation levels and vital signs. The supportive interventions for SARS-CoV-2 infection management include the systematic maintenance of acid-base homeostasis and electrolyte/fluid/energy levels.

Oxygen therapy is required for the patients affected with hypoxemia. The oxygen administration substantiates the requirement of maintaining an oxygen saturation level above 90% in the infected patients. Most importantly, pregnant women affected with SARS-CoV-2 infection require attaining an oxygen saturation level within the range of 92%-95%. COVID-19 patients affected with mild hypoxemia require nasal cannulation at the rate of five liters per minute. However, the intensification of hypoxemia might warrant the enhancement of cannulation rate from 20 liters per minute to 60 liters per minute. Physicians need to monitor and adjust the oxygen fraction following the oxygen saturation maintenance requirement of the treated patient.

What Is the Scope of Non-Invasive Ventilation in COVID-19 Management?

Clinicians recommend the use of non-invasive ventilation only for patients with a high immunity and tolerance level (T, 2020). COVID-19 infected patients who experience critical respiratory complications require endotracheal intubation for invasive ventilation. The trained clinicians require initiating this complex intubation through the systematic use of personal protective equipment. The clinicians must administer extracorporeal membrane oxygenation to the patients affected by severe acute respiratory distress syndrome.

Furthermore, prone positioning for treated patients is a recommended maneuver to reduce the risk of treatment complications (T, 2020). Clinicians need to thoroughly monitor the entire clinical complications that the critically-ill COVID-19 infected patients might experience during their treatment process. The routine application of standard precautions is highly needed to reduce the risk of local transmission during the health care management of SARS-CoV-2 infected patients.

Is There Any Antiviral Treatment available for COVID-19 Management?

The utilization of antiviral therapy for COVID-19 patients is not so far supported by evidence-based clinical literature. However, the administration of ritonavir and/or lopinavir is recommended by some clinicians for a duration of two weeks (T, 2020). The Chinese research centers are on their way to the safety and efficacy testing of favipiravir, remdesivir, arbidol, and chloroquine for COVID-19 infection management (Dong, Hu, & Gao, 2020).

What Is the Scope of Glucocorticoid Therapy in the Clinical Management of COVID-19?

Intravenous administration of methylprednisolone is recommended by some clinicians for COVID-19 management in reliance on the radiological findings and their clinical correlation with the reported symptomatology (T, 2020). Most importantly, the WHO findings provide inclusive evidence regarding the use of glucocorticoids in COVID-19 patients (Russell, Moss, Rigg, & Hemelrijck, 2020). The clinicians might utilize the privilege of using this treatment approach for COVID-19 patients during the acute phase of their disease.

Does Intravenous Immunoglobulin Administration Add Value to COVID-19 Management?

The clinicians recommend the intravenous administration of immunoglobulin for a duration of 3-5 days following the symptomatology of critically ill COVID-19 patients. The study by Cao et al. (2020) reveals satisfactory treatment outcomes in three patients treated with elevated dosages of intravenous immunoglobulin. However, this evidence is still not sufficient to generalize the use of intravenous administration in COVID-19 patients.

Does Empirical Antimicrobial Therapy Influence the Management of COVID-19 Infection?

Oral antibiotics in some clinical scenarios could effectively control the clinical manifestations of community-acquired pneumonia. Some of the research studies reveal the scope of using fluoroquinolones or cephalosporins for resolving COVID-19 symptoms (T, 2020). Evidence-based clinical literature reveals the potential of hydroxychloroquine in challenging the replication of SARS-CoV-2 cells (Singh, Singh, Shaikh, Singh, & Misra, 2020). However, this evidence is only supported by limited in-vitro studies.

The therapeutic efficacy of hydroxychloroquine and its immune-enhancing potential for COVID-19 infected patients is potentially challenged by its adverse effects based on hypoglycemia, dermatological reactions, seizures, and arrhythmias (NIH, 2020). These adverse effects reportedly occur despite the short-term use of hydroxychloroquine in a variety of clinical scenarios. Clinical literature provides inconclusive evidence regarding the effectiveness of sarilumab, tocilizumab, and eculizumab in COVID-19 infection management. However, it is important to note that tocilizumab has the potential to maintain normal body temperature and oxygen saturation requirements of the patients affected with respiratory infections (Singh, Singh, Shaikh, Singh, & Misra, 2020).

The medical community also needs to conduct clinical trials to test the safety and efficacy of clindamycin for COVID-19-based pneumonia. This is because clindamycin effectively treats a range of complicated conditions including skin structure infections, bone/joint infections, gynecological infections, lower respiratory infections, intra-abdominal infections, and septicemia (Murphy & Le, 2020). Similar testing is required for the efficacy of amoxicillin-clavulanic acid combination for the management of respiratory tract infection/pneumonia or other infectious complications in COVID-19 patients (Akhavan & Vijhani, 2020) (Huttner et al., 2019). Clinicians might have the opportunity to use these drugs or their combinations for COVID-19 infection management based on the findings of prospective clinical trials.

What Is the Scope of Integrative Medicine in Treating COVID-19 Infection?

Evidence-based literature provides some evidence related to the effectiveness of integrative medicine in the systematic management of COVID-19 cases. The combinations of allopathic medicine and traditional Chinese herbal medicine are widely discussed in the context of their potential to treat SARS-CoV-2 infection. The study by Wang, Chen, Lu, Chen, and Zhang (2020) reveals the therapeutic advantage of integrative therapy based on Shufeng Jiedu capsule, arbidol, and ritonavir/lopinavir for COVID-19 infected patients.

Andrew Weil Center for Integrative Medicine advocates the use of vitamin D for the enhancement of brain function, bone health, and immune system (Integrative Medicine Arizona, 2020). However, the center recommends the discontinuation of vitamin D by the COVID-19 infected patients based on its potential to activate inflammatory pathways. The center, however, provides some clues regarding the use of herbs like elderberry and Boswellia serrata for COVID-19 prophylaxis based on their anti-inflammatory properties. Clinical trials are, however, necessarily required to evaluate the use of these herbs with mainstream pharmacotherapy in COVID-19 infected patients.

References

Akhavan, B. J., & Vijhani, P. (2020). StatPearls. In Amoxicillin. Treasure Island (Florida): StatPearls Publishing.

Bandyopadhyay , S. (2020). Coronavirus Disease 2019 (COVID-19): we shall overcome. Clean Technologies and Environmental Policy, 1-2. doi:10.1007/s10098-020-01843-w

Cao, W., Liu, X., Bai, T., Fan, H., Hong, K., Song, H., . . . Li, T. (2020). High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019. Open Forum Infectious Diseases, 7(3). doi:10.1093/ofid/ofaa102

Cascella, M., Rajnik, M., Cuomo, A., Dulebohn, S. C., & Napoli, R. D. (2020). Features, Evaluation and Treatment Coronavirus (COVID-19). In StatPearls [Internet]. Treasure Island (Florida): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK554776/

Chin, A. W., Chu, J. T., Perera, M. R., Hui, K. P., Yen, H. L., Perera, M. C., . . . Poon, L. L. (2020). Stability of SARS-CoV-2 in different environmental conditions. The Lancet. doi:https://doi.org/10.1016/S2666-5247(20)30003-3

Dong, L., Hu, S., & Gao, J. (2020). Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discoveries & Therapeutics, 14(1), 58-60. Retrieved from https://www.jstage.jst.go.jp/article/ddt/14/1/14 2020.01012/ article

Fisher, D., & Heymann, D. (2020). Q&A: The novel coronavirus outbreak causing COVID-19. BMC Medicine, 18(57), 1-3. doi:10.1186/s12916-020-01533-w

Huttner, A., Bielicki , J., Clements , M. N., Frimodt-Møller , N., Muller , A. E., Paccaud , J. P., & Mouton , J. W. (2019). Oral amoxicillin and amoxicillin-clavulanic acid: properties, indications and usage. Clinical Microbiology and Infection. doi:10.1016/j.cmi.2019.11.028

Integratitve Medicine Arizona. (2020). COVID-19 FAQ. Retrieved from https://integrativemedicine.arizona.edu/COVID19/FAQ.html

Li, T. (2020). Diagnosis and clinical management of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection: an operational recommendation of Peking Union Medical College Hospital (V2.0)-Working Group of 2019 Novel Coronavirus, Peking Union Medical Colleg. Emerging Microbes and Infections, 582-585. doi:10.1080/22221751.2020.1735265

Murphy, P. B., & Le, J. K. (2020). Clindamycin. In StatPearls. Treasure Island (Florida): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK519574/

NIH. (2020, 04 09). NIH clinical trial of hydroxychloroquine, a potential therapy for COVID-19, begins. Retrieved from https://www.nih.gov/news-events/news-releases/nih-clinical-trial-hydroxychloroquine-potential-therapy-covid-19-begins

Russell, B., Moss, C., Rigg, A., & Hemelrijck, M. V. (2020). COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting? Ecancermedicalscience. doi:10.3332/ecancer.2020.1023

Singh, A. K., Singh, A., Shaikh, A., Singh, R., & Misra, A. (2020). Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes and Metabolic Syndrome, 14(3), 241-246. doi:10.1016/j.dsx.2020.03.011

T, L. (2020). Diagnosis and clinical management of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection: an operational recommendation of Peking Union Medical College Hospital (V2.0). Emerging Microbes and Infections, 9(1), 582-585. doi:10.1080/22221751.2020.1735265

Tahirul-Qamar, M., Alqahtani, S. M., Alamri , M. A., & Chen, L. L. (2020). Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. Journal of Pharmaceutical Analysis. Retrieved from https://www.sciencedirect.com/science/article/pii/S2095177920301271

Wang, C., Pan, R., Wan, X., Tan, Y., Xu, L., Ho, C. S., & Ho, R. C. (2020). Immediate Psychological Responses and Associated Factors during the Initial Stage of the 2019 Coronavirus Disease (COVID-19) Epidemic among the General Population in China. International Journal of Environmental Research and Public Health, 17(5). doi:10.3390/ijerph17051729

Wang, Z., Chen, X., Lu, Y., Chen, F., & Zhang, W. (2020). Clinical characteristics and therapeutic procedure for four cases. BioScience Trends, P1-P5. doi:10.5582/bst.2020.01030

This content is for informational purposes only and does not substitute for formal and individualized diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed medical professional. Do not stop or alter your current course of treatment. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2020 Dr Khalid Rahman

Discussion

Dr Khalid Rahman (author) from India on April 23, 2020:

Dear Mr. Lyndon Henry:

Thanks for your feedback and valuable inputs.

Lyndon Henry from Central Texas on April 23, 2020:

An excellent, comprehensive, competent presentation of crucial factual information regarding this extraordinarily dangerous disease. My congratulations, and thanks, for this superb resource.

Mariyam Ahmed on April 09, 2020:

Very nice article,you have been sharing your knowledge to the world. Excellent!!!! Good job !!!!!!!!!!!!!!!!!!! I liked your article a lot .

Sarah on April 09, 2020:

Excellent!! Good luck!! Their are so many therapys that i was so much confused!! I learned so many things. Very nice article about coronavirus. Thank you for sharing your knowledge to everyone. Thanks.