Results of Clinical Trials for Remdesivir, Chloroquine, Lopinavir/Ritonavir, and Arbidol to Treat Patients with COVID-19

By | Uncategorized | No Comments

 

 

 

 

 

COVID-19 has become the most pressing global public health crisis in decades, with more than 3.6 million cases recorded in the United States alone as of the writing of this article. The biggest challenge of the pandemic is the novelty of this coronavirus and the absence of an approved drug or vaccine. Under extreme time pressure to treat patients with severe symptoms, several pre-existing drugs including remdesivir, chloroquine, lopinavir/ritonavir, and arbidol have caught the attention of researchers. Clinical trials were conducted in the hopes that they show clinical efficacy against the highly infectious SARS-CoV-2 strain.

 

Remdesivir is an adenosine analogue prodrug that inhibits viral RNA polymerases, including SARS-CoV-2 in vitro1.Although not FDA-approved to treat COVID-19, healthcare providers have initiated compassionate use of remdesivir for patients with confirmed SARS-CoV-2 and low oxygen saturation. In a cohort study published in April, researchers administered a 10-day course of intravenous remdesivir to patients with COVID-19 and reported clinical improvement in 36 of 53 patients (68%)2. This study showed promise for the use of remdesivir but lacked a control group to conclude the efficacy of the drug. In another trial reported in May, researchers conducted a randomized, double-blind, placebo-controlled trial with 236 patients. However, the results of this particular trial showed no significant difference between clinical improvement rates of the remdesivir group and placebo group3. The results of the most recent phase three trial conducted by Gilead indicated that the 5-day remdesivir course group was 65% more likely to have clinical improvement compared to the control group, which only received standard care. The 10-day remdesivir course group did not show statistical significance when compared to the control group4.

 

Chloroquine is another example of a drug that quickly gained interest during the early days of the pandemic. It is normally used to treat malaria and arthritis, and its antiviral effects have resulted in its administration to patients with COVID-19 without much evidence of clinical efficacy. In an observational study, researchers followed 1376 patients at a medical center in New York City and compared the results between those who received hydroxychloroquine and those who did not. The study concluded that there was no significant difference between the two groups5. The Recovery trial run by Oxford University followed a greater sample size, but ultimately also issued a statement announcing that chloroquine has no beneficial effect when used to treat COVID-196. FDA has also cautioned use of chloroquine due to side effects such as serious heart rhythm problems7.

 

Lopinavir and ritonavir are combined antiretroviral medications used to control HIV infection. A randomized, controlled study published in May assigned 199 patients to either the lopinavir-ritonavir group or the control group that only received standard care. Mortality rates at 28 days for the experimental group was slightly but not significantly lower than the control group. The percentage of patients with detectable viral RNA was similar in both groups. Ultimately, it was concluded that use of lopinavir and ritonavir did not provide any benefits for treating COVID-198. WHO announced in July that it would discontinue its hydroxychloroquine and lopinavir/ritonavir trials due to evidence that neither of these medications benefit patients with COVID-199.

 

Arbidol is commonly used in China and Russia to treat influenza by blocking virus-cell membrane fusion10. Li et al. conducted a randomized trial with 35 patients who received arbidol orally and 17 who received no antiviral medication. The rate of positive-to-negative conversion of SARS-CoV-2 nucleic acid was similar in both groups. The arbidol group exhibited adverse effects, while the control group did not. Arbidol presented no benefit to patients with COVID-1911.On the other hand, another study concluded that arbidol significantly reduced COVID-19 infection among health professionals. Arbidol may not be effective in treating COVID-19, but this study sheds light on its possible preventative abilities12.

 

No therapeutics have been proven to effectively treat COVID-19 at this stage, but studies are taking place globally to further explore the efficacy of the drugs mentioned.

 

 

 

References:

 

 

  1. Sheahan TP, Sims AC, Graham RL et al. (2017). Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med.

 

  1. Grein, Jonathan, et al. (2020). Compassionate Use of Remdesivir for Patients with Severe Covid-19. New England Journal of Medicine, vol. 382, no. 24, pp. 2327–2336. doi:10.1056/nejmoa2007016.

 

  1. Wang, Yeming, et al. (2020). Remdesivir in Adults with Severe COVID-19: a Randomised, Double-Blind, Placebo-Controlled, Multicentre Trial. The Lancet, vol. 395, no. 10236, pp. 1569– 1578. doi:10.1016/s0140-6736(20)31022-9.

 

  1. Gilead Announces Results From Phase 3 Trial of Remdesivir in Patients With Moderate COVID-19. (2020) Gilead, Gilead Sciences.

 

  1. Geleris, Joshua, et al. (2020). Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19. New England Journal of Medicine, vol. 382, no. 25, pp. 2411–2418. doi:10.1056/nejmoa2012410.

 

 

  1. No Clinical Benefit from Use of Hydroxychloroquine in Hospitalised Patients with COVID-19 (2020) RECOVERY Trial.

 

  1. Center for Drug Evaluation and Research. FDA Cautions Use of Hydroxychloroquine/Chloroquine for COVID-19. (2020). U.S. Food and Drug Administration, FDA

 

  1. Cao, Bin, et al. (2020). A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. New England Journal of Medicine, vol. 382, no. 19, pp. 1787–1799. doi:10.1056/nejmoa2001282

 

  1. WHO Discontinues Hydroxychloroquine and Lopinavir/Ritonavir Treatment Arms for COVID-19. World Health Organization, 4 July 2020

 

  1. Villalaín J. (2010). Membranotropic effects of arbidol, a broad anti-viral molecule, on phospholipid model membranes. J Phys Chem B. 2010;114(25):8544–8554. doi:10.1021/jp102619w.

 

  1. Li, Yueping, et al. (2020). Efficacy and Safety of Lopinavir/Ritonavir or Arbidol in Adult Patients with Mild/Moderate COVID-19: An Exploratory Randomized Controlled Trial. Med, doi:10.1016/j.medj.2020.04.00

 

 

  1. Yang, Chunguang, et al. (2020). Effectiveness of Arbidol for COVID-19 Prevention in Health Professionals. Frontiers in Public Health, vol. 8, 2020, doi:10.3389/fpubh.2020.00249.

The Effects of Medical School Debt

By | Uncategorized | No Comments

In 1984, 86% of medical students graduated with some amount of debt. While that number has not increased significantly over the past three-and-a-half decades, the amount of debt owed by each individual graduate has increased significantly even when adjusted for inflation, according to Greyson, et. al [1]. In 2012, medical school debt had reached a mean of $158,000 [2]. By 2016, the average medical school graduate owed $190,000, with some residents owing as much as $500,000 [3]. Furthermore, many residents still have unpaid debt from their undergraduate degrees when they finish medical school [4]. 

This debt creates three primary problems for the medical field as a whole. Firstly, debt discourages students from underrepresented backgrounds from attending medical school. In the first half of the twentieth century, Black students constituted only 2-3% of enrollment at American medical schools. Between 1950 and 1973, that number grew exponentially. However, since 1973, racial diversity has plateaued [1]. Moreover, in 2004, only 10% of medical students came from households in the lowest two quintiles of nationwide income. This represents a decrease of 17% since 1971 [1].  

To address this problem, some medical schools have started offering large scholarships to underrepresented groups or have decided to abolish tuition entirely. Columbia University’s Irving Medical Center received a $150 million gift in 2017, which allowed 20% of its students to attend for free, with another 30% receiving significant scholarships [4]. Similarly, in 2018, NYU announced that its medical school would become tuition-free, which it lauded as a way to nurture diversity [5].  

According to Steiner, et.al., the rise in debt also affects the disciplines that medical students choose. This leads to fewer students pursuing lower income specialties like pediatrics, which typically pays between $150,000 and $200,000 yearly. In a survey of over 500 anesthesiology residents, those with a higher-than-average amount of debt were 7% less likely to self-report as interested in an academic career. Moreover, these residents reported more interest in working at private practices that offered debt repayment programs [3]. In addition to influencing the chosen fields of medical students, debt affects the locations in which they choose to practice, leading to a lack of doctors in rural or underserved areas. States where high percentages of residents rely on Medicaid find it difficult to attract physicians, leading one such state, California, to develop a debt relief program for doctors who accept Medicaid [6]. 

Finally, medical residents with large amounts of debt are more likely to take on extra work and report higher rates of emotional stress. The above survey of anesthesiology residents found that those with higher-than-average debt were not only less likely to choose a career in academics but were also 7% more interested in moonlighting during residency or fellowship [3]. In a survey of 3,000 American medical students by Rohlfing, et.al., those with more debt reported more incidents of acting callously towards others than those with less debt. These students were also more likely to report regret about pursuing medicine [7]. Steady increases in medical school debt have influenced the diversity of medical schools, students’ choice of field, and the well-being of medical students, residents, and fellows. In response, states, philanthropists, and universities have responded by establishing debt-relief programs and scholarships, and in some cases by eliminating tuition entirely.  

 

References  

[1] Greysen, S. Ryan, et al. “A History of Medical Student Debt: Observations and Implications for the Future of Medical Education.” Academic Medicine, vol. 86, no. 7, 2011, pp. 840–845., doi:10.1097/acm.0b013e31821daf03. 

[2] Steiner, Jeffrey W., et al. “Anesthesiology Residents’ Medical School Debt Influence on Moonlighting Activities, Work Environment Choice, and Debt Repayment Programs.” Survey of Anesthesiology, vol. 56, no. 6, 2012, p. 281., doi:10.1097/01.sa.0000422040.29757.47. 

[3] Grischkan, Justin, et al. “Distribution of Medical Education Debt by Specialty, 2010-2016.” JAMA Internal Medicine, vol. 177, no. 10, 2017, p. 1532., doi:10.1001/jamainternmed.2017.4023. 

[4] Glauser, Wendy. “How Medical School Debt Shapes the Health Workforce.” Canadian Medical Association Journal, vol. 190, no. 29, 2018, doi:10.1503/cmaj.109-5607. 

[5] Thomas, Billy. “Free Medical School Tuition.” Jama, vol. 321, no. 2, 2019, p. 143., doi:10.1001/jama.2018.19457. 

[6] Rueb, Emily S., and Karen Zraick. “Doctors in Debt: These Physicians Gladly Struck a Deal With California.” The New York Times, The New York Times, 25 July 2019, www.nytimes.com/2019/07/25/health/california-medical-student-loans.html. 

[7] Rohlfing, James, et al. “Medical Student Debt and Major Life Choices Other than Specialty.” Medical Education Online, vol. 19, no. 1, 2014, p. 25603., doi:10.3402/meo.v19.25603. 

Nonlinear Dynamics of Heart Rate Variability

By | Uncategorized | No Comments

The study of dynamical systems has the goal of describing the evolution of interconnected variables over time. Non-linear systems are the subject of extensive study because they accurately model many natural phenomena and because they are mathematically intractable. Except in rare cases, the future states of non-linear systems are hard to predict, but knowing the future states is the goal of studying the system. Chaotic systems are non-linear systems that demonstrate aperiodic behavior sensitive to initial conditions. They are often particularly well-suited to describing many natural phenomena, including heart-rate variability, and mathematicians have developed powerful tools for studying them.   

Chaotic systems often involve the interplay of so many variables that the evolution of the system appears stochastic (random) but is in fact deterministic. Classifying a system as one or the other determines the type of analysis appropriate for understanding the system. Heartrate is an example of a system that demonstrates both types of behavior. Doctors study heartrate because the heartbeat pattern allows them to indirectly and non-invasively predict and diagnose pathophysiological conditions.1 For example, the peaks and troughs on a heartrate tachogram can indicate mortality risk in cardiac patients. Traditionally, heartrate tachogram analysis was done with time-series models, which assume that the system is stochastic instead of chaotic. These traditional methods are insufficient in many cases like congestive heart failure, which has a distinct chaotic signature separate from the random signatures related to health and aging.2 The pattern of the heartbeat appears random, but in reality is deterministic, which allows for a whole new class of analysis.  

Non-linear methods outperform linear methods in explaining changes in the heartbeat interval because they can detect patterns that linear methods cannot. Young and Benton showed that only after measuring heart-rate complexity with non-linear methods was a model of heart-rate behavior statistically significantly related to depression, focused attention reaction times, and perceived stress and anxiety. They also showed that the added heart-rate complexity was necessary to show a difference between the behavior of females and males.3 Another study showed that qualitative measures of state anxiety were positively correlated with a loss in the complexity of heart-rate variability.4  

The complexity of the heartbeat refers to the dimension of the dynamical system required to best model the observed signal. An entirely stochastic heartbeat would have infinite dimension. A periodic heartbeat would have dimension one. The signal captured by the non-linear dynamics of the heartbeat more accurately reflects the deep complexity of the process the body undertakes when regulating the heartbeat. Linear measures such as variability can differentiate between old and young, but cannot capture the richness of the signal needed for doctors to infer sinister underlying conditions.5 

 

 References 

 

(1) Shiogai Y., Stefanovska A., McClintock P. V. E. (2010). Nonlinear dynamics of cardiovascular ageing. Phys. Rep. 488, 51–110. 10.1016/j.physrep.2009.12.003, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2853263/. 

 

(2) Wu, Guo-Qiang, et al. “Chaotic Signatures of Heart Rate Variability and Its Power Spectrum in Health, Aging and Heart Failure.” PloS One, Public Library of Science, 2009, www.ncbi.nlm.nih.gov/pmc/articles/PMC2629562/. 

 

(3) Hayley Young, and David Benton. “We Should Be Using Nonlinear Indices When Relating Heart-Rate Dynamics to Cognition and Mood.” Nature News, Nature Publishing Group, 13 Nov. 2015, www.nature.com/articles/srep16619. 

 

(4) Dimitriev, Dimitriy A., et al. “State Anxiety and Nonlinear Dynamics of Heart Rate Variability in Students.” PLOS ONE, Public Library of Science, 26 Jan. 2016, journals.plos.org/plosone/article?id=10.1371\%2Fjournal.pone.0146131. 

 

(5) Kaplan DT, Furman MI, Pincus SM, Ryan SM, Lipsitz LA, Goldberger AL. Aging and the complexity of cardiovascular dynamics. Biophys J. 1991;59(4):945‐949. doi:10.1016/S0006-3495(91)82309-8, https://core.ac.uk/download/pdf/82722142.pdf.

Anesthetic Management of Sports Injuries

By | Uncategorized | No Comments

In an age where many Americans have a sedentary lifestyle, taking the time to exercise is important to overall health and well-being.1 Exercise helps control weight, reduces risk of heart disease and some cancers, helps the body manage blood sugar and insulin levels, makes smoking cessation easier, improves mental health and mood, helps maintain thinking and learning skills while aging, strengthens bones and muscles, reduces risk of falls, improves sleep, improves sexual health and increases longevity.1 Participation in sports can have benefits beyond exercise, in that it boosts self-esteem and create friendships.2 However, exercise and sports can also cause physical injuries.3 Sometimes, the diagnosis and/or treatment of a sports injury can be invasive, involving surgery or another inpatient procedure.4,5 Given that many sports injuries can be painful and require aggressive treatments, anesthesia providers should be familiar with the most common types of sports injuries and their role in diagnosis or treatment. 

 

Sports injuries can develop from accidents; poor training practices, such as overtraining or increasing training too quickly; use of improper gear; and lack of warming up or stretching.3 The most common sports injuries are sprains and strains, knee injuries, swollen muscles, Achilles tendon injuries, shin pain, rotator cuff injuries, fractures and dislocations.3 Initial treatment often entails the RICE (rest, ice, compression and elevation) method to reduce pain and swelling and speed healing.3 Other pain relief and treatment options include taking pain medication such as acetaminophen, ibuprofen or other nonsteroidal anti-inflammatory drugs (NSAIDs); immobilizing the injured area; getting physical therapy or massage; using corticosteroid injections; and surgery.6 Injury types may vary by age, sport and gender, but common injuries include head injuries, fractures, anterior cruciate ligament (ACL) and injuries and ankle sprains.7-10 Female athletes present with more bone stress injuries (BSIs) and male athletes may be less likely to report concussions.8 Older patients may be more likely than young patients to show knee injuries or inflammatory conditions.7 Injuries can also vary widely in extent, cause and necessary treatment.8 For athletes whose identities are tied to physical ability, long-term sports injuries can have extensive psychological effects.11 Given the range of injuries across sports, genders, ages and causes, clinicians must be prepared for an array of patient experiences.  

 

Given their expertise in pain management and anesthetic drugs, anesthesiology practitioners are often crucial to the diagnosis and treatment of sports injuries. In a study by Kulacoglu et al., clinicians used anterior inguinal exploration with local anesthesia to assess chronic groin pain in soccer players.12 Through this slightly invasive procedure, clinicians were able to distinguish between posterior inguinal floor weakness (“sports hernia”), osteitis pubis (inflammatory disease of the pubic area), rectus abdominis injury, adductor tendon injury or pelvic stress fracture.12 Dahlstedt and Dalén examined patients’ knee stability under general or epidural anesthesia to help diagnose ACL injuries.13 Meanwhile, Dezawa et al. performed minimally invasive surgery to release the piriformis muscle under local anesthesia, which ultimately led to the patient’s recovery from painful piriformis syndrome.4 Foster et al.’s study of overall United States hospital practices found that the use of general anesthesia alone was most common for ACL reconstruction surgery.5 However, between 2004 and 2009, there was a slight increase in the use of general anesthesia in combination with regional anesthesia or single femoral nerve injection.5 Regional anesthesia alone was only used in one percent of 53,968 arthroscopic ACL reconstructive procedures.5 According to a paper by Üzümcügil et al., anesthesia may be necessary in the emergency department or prehospital setting for procedural preparation and pain management.14 This includes administration of peripheral nerve blocks, sedation and other forms of analgesia.14 The authors state that if the injury necessitates surgery, combinations of anesthetic techniques and postoperative pain management should aim to hasten recovery, facilitate rehabilitation and accelerate the return to the sport.14 Athletes’ determination and sometimes financial need to return to a sport encourages the use of local anesthetics for injury pain.15 A study by Kannus et al. from 30 years ago found that long-acting bupivacaine was a useful anesthetic in combination with local steroid injections for musculoskeletal overuse injuries.16 More recent papers show some concern about local anesthetic injections depending on length of use and location. Nepple and Matava’s review shows that the primary concern associated with local anesthetic injections is an increased risk of tendon rupture.17 Additionally, injection of ketorolac tromethamine, an analgesic NSAID, can increase risk of bleeding.17 Orchard et al.’s survey of rugby players found that local anesthetic injections to acromioclavicular joint sprains, finger and rib injuries and iliac crest contusions appeared to be safe, while ankle, wrist and sternum injections led to worsened injuries after playing.18 Some clinicians wonder if local anesthetic injection for quick return to play is in the long-term best interest of the patient.15 Evidently, anesthesia has various applications to diagnosis and treatment of sports injuries, with some uses being more controversial than others. 

 

Sports can be beneficial to one’s mental and physical health, but they can also lead to painful and chronic injuries such as stress fracture, ACL tears and joint issues. Anesthesia providers can help in the diagnosis and treatment of sports injuries through administering anesthesia during surgical procedures and for pain relief. More research is needed to determine the long-term effects of using local anesthetics to return quickly to a sport.  

 

1.Benefits of Exercise. MedlinePlus. Bethesda, MD: U.S. National Library of Medicine; August 30, 2017. 

2.University of Missouri. Benefits of Sports for Adolescents. MU Health Care 2020; https://www.muhealth.org/conditions-treatments/pediatrics/adolescent-medicine/benefits-of-sports. 

3.Sports Injuries. MedlinePlus. Bethesda, MD: U.S. National Library of Medicine; January 2, 2017. 

4.Dezawa A, Kusano S, Miki H. Arthroscopic release of the piriformis muscle under local anesthesia for piriformis syndrome. Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2003;19(5):554–557. 

5.Foster BD, Terrell R, Montgomery SR, Wang JC, Petrigliano FA, McAllister DR. Hospital Charges and Practice Patterns for General and Regional Anesthesia in Arthroscopic Anterior Cruciate Ligament Repair. Orthopaedic Journal of Sports Medicine. October 2013;1(5):1–5. 

6.National Health Service. Treatment. Sports injuries March 21, 2017; https://www.nhs.uk/conditions/sports-injuries/treatment/. 

7.DeHaven KE, Lintner DM. Athletic injuries: Comparison by age, sport, and gender. The American Journal of Sports Medicine. 1986;14(3):218–224. 

8.Lin CY, Casey E, Herman DC, Katz N, Tenforde AS. Sex Differences in Common Sports Injuries. PM&R. 2018;10(10):1073–1082. 

9.Brant JA, Johnson B, Brou L, Comstock RD, Vu T. Rates and Patterns of Lower Extremity Sports Injuries in All Gender-Comparable US High School Sports. Orthopaedic Journal of Sports Medicine. 2019;7(10):7. 

10.Monroe KW, Thrash C, Sorrentino A, King WD. Most Common Sports-Related Injuries in a Pediatric Emergency Department. Clinical Pediatrics. 2010;50(1):17–20. 

11.Heil J. Psychology of Sport Injury. Champaign, IL: Human Kinetics Publishers; 1993. 

12.Kulacoglu H, Ozyaylali I, Kunduracioglu B, Yazicioglu D, Ersoy E, Ugurlu C. The Value of Anterior Inguinal Exploration With Local Anesthesia for Better Diagnosis of Chronic Groin Pain in Soccer Players. Clinical Journal of Sport Medicine. 2011;21(5):456–459. 

13.Dahlstedt LJ, Dalén N. Knee laxity in cruciate ligament injury: Value of examination under anesthesia. Acta Orthopaedica Scandinavica. 1989;60(2):181–184. 

14.Üzümcügil F, Saricaoglu F, Aypar Ü. Anesthesia Managements for Sports-Related Musculoskeletal Injuries. In: Doral MN, Karlsson J, eds. Sports Injuries: Prevention, Diagnosis, Treatment and Rehabilitation. Berlin, Heidelberg: Springer Berlin Heidelberg; 2015:2159–2169. 

15.Hughes C. Local anesthetic use in sport for early return to play – should we be offering these jabs? Clinical Journal of Sport Medicine Blog January 13, 2012; https://cjsmblog.com/2012/01/13/local-anesthetic-use-in-sport-for-early-return-to-play-should-we-be-offering-these-jabs/. 

16.Kannus P, Jarvinen M, Niittymaki S. Long- or short-acting anesthetic with corticosteroid in local injections of overuse injuries? A prospective, randomized, double-blind study. International Journal of Sports Medicine. 1990;11(5):397–400. 

17.Nepple JJ, Matava MJ. Soft tissue injections in the athlete. Sports Health. 2009;1(5):396–404. 

18.Orchard JW, Steet E, Massey A, Dan S, Gardiner B, Ibrahim A. Long-term safety of using local anesthetic injections in professional rugby league. American Journal of Sports Medicine. 2010;38(11):2259–2266. 

 

The Epidemiology of SARS-CoV-2

By | Uncategorized | No Comments

The recent outbreak of coronavirus (COVID-19) has turned into a public health emergency of international concern. With no antiviral drugs or vaccines, and the presence of carriers without obvious symptoms, traditional public health intervention measures are now significantly less effective (1). The pandemic began in late December 2019, when a cluster of patients was admitted to hospitals with an initial diagnosis of pneumonia of an unknown etiology. These patients were epidemiologically linked to a seafood and wet animal wholesale market in Wuhan, Hubei Province, China (2). The timeline of the initial outbreak can be divided into three phases. The local outbreak by exposure in the aforementioned food wholesale market marks the first phase. The second phase started on January 13 and was marked by rapid expansion and spread of the virus within hospitals (nosocomial infection) and by family transmission (close-contact transmission). In this phase, the epidemic spread from Wuhan to other areas. The first case outside of China was reported in Thailand on January 13, caused by a Wuhan resident travelling to this country. Already by January 23, 29 provinces within China, plus six foreign countries, had reported a total of 846 confirmed cases, an approximately 20-fold increase from the first phase. Meanwhile, Wuhan implemented a ‘lock-down’ (i.e., shutting down all movement within and out of the city). Unfortunately, this period coincided with the traditional mass movement of people, a form of ‘home-coming’, before Chinese New Year and thus more than 5 million people had already left Wuhan (1). The third phase started on January 26, and four days later the outbreak was designated a Public Health Emergency of International Concern by WHO. By February 12, newly confirmed cases in China jumped to 14,840. By that time, 25 countries had reported over 60,000 infections (1). Of note, February 3 seems to be a tipping point of the epidemic in China, from which time the daily number of confirmed cases outside Hubei began to decline. Whether it reflects the success of the ‘Wuhan lock-down’ and other public health measures, or virus transmission reduced for other reasons, remains unclear (1). As of March 31, more than 800,000 confirmed cases of COVID-19 have been reported. Although the outbreak began in China, the US, Italy, and Spain all now have more confirmed cases. In particular, the US has nearly 180,000 cases and over 3,400 deaths (compared to ~80,000 cases and ~3,300 deaths in China) (3).

 

COVID-19 has been found to have higher levels of transmissibility and pandemic risk than the SARS-CoV, as the effective reproductive number (R) of COVID-19 (2.9) is estimated to be higher than the reported R of SARS (1.77) at this early stage (4). However, it is worth noting that R estimates may vary upon numerous biological, socio-behavioral, and environmental factors, and must be interpreted with caution (1). Person-to-person spread of COVID-19 is thought to occur mainly via respiratory droplets, resembling the spread of influenza. With droplet transmission, virus released in the respiratory secretions when a person with infection coughs, sneezes, or talks can infect another person if it makes direct contact with the mucous membranes; infection can also occur if a person touches an infected surface and then touches his or her eyes, nose, or mouth. Droplets typically do not travel more than six feet (about two meters) and do not linger in the air. However, given the current uncertainty regarding transmission mechanisms, airborne precautions are recommended routinely in some countries and in the setting of certain high-risk procedures in others (4).

 

The interval during which an individual with COVID-19 is infectious is also uncertain. Most data informing this issue are from studies evaluating viral RNA detection from respiratory and other specimens. However, detection of viral RNA does not necessarily indicate the presence of infectious virus. Viral RNA levels appear to be higher soon after symptom onset compared with later in the illness, which raises the possibility that transmission might be more likely in the earlier stage of infection, but additional data is needed to confirm this hypothesis. The duration of viral shedding is also variable; there appears to be a wide range, which may depend on severity of illness. In one study of 137 patients who survived COVID-19, the median duration of viral RNA shedding from oropharyngeal specimens was 20 days (range of 8 to 37 days) (4). Transmission of SARS-CoV-2 from asymptomatic individuals (or individuals within the incubation period) has also been described. However, the extent to which this occurs remains unknown. Large-scale serologic screening may be able to provide a better sense of the scope of asymptomatic infections and inform epidemiologic analysis; several serologic tests for SARS-CoV-2 are under development to help provide a better sense of the scope of asymptomatic infections and inform epidemiologic analysis (4).

 

Extensive measures to reduce person-to-person transmission of COVID-19 are required to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people (2). The early death cases of COVID-19 outbreak occurred primarily in elderly people, possibly due to a weak immune system that permits faster progression of viral infection. Public services and facilities should provide decontaminating reagents for cleaning hands on a routine basis. Physical contact with wet and contaminated objects should be considered in dealing with the virus, especially agents such as fecal and urine samples that can potentially serve as an alternative route of transmission. China and other countries including the US have implemented major prevention and control measures including travel screenings to control further spread of the virus. Epidemiological changes in COVID-19 infection should be monitored, taking into account potential routes of transmission and subclinical infections, in addition to the adaptation, evolution, and virus spread among humans and possible intermediate animals and reservoirs (2)

 

References

 

  1. Sun J, He W, Wang L, et al. COVID-19: epidemiology, evolution, and cross-disciplinary perspectives. Trends Mol Med. 2020. Epub ahead of print.
  2. Rothan HA, Byrareddy SN: The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020:102433-102433. 10.1016/j.jaut.2020.102433
  3. COVID-19 CORONAVIRUS PANDEMIC. (n.d.). Retrieved March 31, 2020, from https://www.worldometers.info/coronavirus/
  4. McIntosh, K. (2020, March 25). Coronavirus disease 2019 (COVID-19). Retrieved March 31, 2020, from https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19