Treatment and management of COVID-19

Last updated

There is no specific, effective treatment or cure for coronavirus disease 2019 (COVID-19), the disease caused by the SARS-CoV-2 virus. [1] [ needs update ] [2] One year into the pandemic, highly effective vaccines have now been introduced and are beginning to slow the spread of SARS-CoV-2; however, for those awaiting vaccination, as well as for the estimated millions of immunocompromised persons who are unlikely to respond robustly to vaccination, treatment remains important. [3] Thus, the lack of progress developing effective treatments means that the cornerstone of management of COVID-19 has been supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support and prone positioning as needed, and medications or devices to support other affected vital organs. [4] [5] [6]

Contents

Most cases of COVID-19 are mild. In these, supportive care includes medication such as paracetamol or NSAIDs to relieve symptoms (fever, body aches, cough), proper intake of fluids, rest, and nasal breathing. [7] [2] [8] [9] Good personal hygiene and a healthy diet are also recommended. [10] The U.S. Centers for Disease Control and Prevention (CDC) recommend that those who suspect they are carrying the virus isolate themselves at home and wear a face mask. [11]

People with more severe cases may need treatment in hospital. In those with low oxygen levels, use of the glucocorticoid dexamethasone is strongly recommended, as it can reduce the risk of death. [12] [13] [14] Noninvasive ventilation and, ultimately, admission to an intensive care unit for mechanical ventilation may be required to support breathing. [15] Extracorporeal membrane oxygenation (ECMO) has been used to address the issue of respiratory failure, but its benefits are still under consideration. [16] [17] Some of the cases of severe disease course are caused by systemic hyper-inflammation, the so called cytokine storm. [18]

Several experimental treatments are being actively studied in clinical trials. [1] These include fluvoxamine, a cheap and widely available antidepressant; [19] and the antivirals molnupiravir (developed by Merck), [20] and PF-07321332 (developed by Pfizer). [21] Others were thought to be promising early in the pandemic, such as hydroxychloroquine and lopinavir/ritonavir, but later research found them to be ineffective or even harmful. [1] [22] [23] Despite ongoing research, there is still not enough high-quality evidence to recommend so-called early treatment. [22] [23] Nevertheless, in the United States, two monoclonal antibody-based therapies are available for early use in cases thought to be at high risk of progression to severe disease. [23] The antiviral remdesivir is available in the U.S., Canada, Australia, and several other countries, with varying restrictions; however, it is not recommended for people needing mechanical ventilation, and is discouraged altogether by the World Health Organization (WHO), [24] due to limited evidence of its efficacy. [1] In November 2021, the UK approved the use of Molnupiravir as a Covid treatment for vulnerable patients recently diagnosed with the disease. [25]

Some people may experience persistent symptoms or disability after recovery from the infection; this is known as long COVID. There is still limited information on the best management and rehabilitation for this condition. [15]

The WHO, the Chinese National Health Commission, the UK National Institute for Health and Care Excellence, and the United States' National Institutes of Health, among other bodies and agencies worldwide, have all published recommendations and guidelines for taking care of people with COVID‑19. [26] [27] [15] [28] Intensivists and pulmonologists in the U.S. have compiled treatment recommendations from various agencies into a free resource, the IBCC. [29] [30]

Medications

An exhausted anesthesiologist physician in Pesaro, Italy, March 2020 Covid-19 San Salvatore 09.jpg
An exhausted anesthesiologist physician in Pesaro, Italy, March 2020

A large number of drugs have been considered for treating COVID-19 patients. [31] As of February 2021, in the United States, remdesivir has FDA approval for certain COVID-19 patients, so far the first only drug to achieve that permission. [32] There are Emergency Use Authorizations for baricitinib, bamlanivimab, bamlanivimab/etesevimab, and casirivimab/imdevimab. [33] On 16 April 2021, the FDA revoked the emergency use authorization (EUA) that allowed for the investigational monoclonal antibody therapy bamlanivimab, when administered alone, to be used for the treatment of mild-to-moderate COVID-19 in adults and certain pediatric patients. [34] In the European Union, the use of dexamethasone is endorsed, and remdesivir has a conditional marketing authorisation. [35] Despite being controversial at the beginning of the pandemic, [36] corticosteroids like Dexamethasone have ultimately showed clinical benefit in treating COVID-19, once randomized controlled trials were performed on them. [37] [38] Specifically, there is moderate‐certainty evidence suggesting that dexamethasone, and systemic corticosteroids in general, probably cause a slight reduction in all‐cause mortality in hospitalised patients suffering COVID‐19. [39] Early research suggested a benefit of remdesivir in preventing death and shortening illness duration, but this was not borne out by subsequent trials. [1] Other drugs such as budesonide and tocilizumab have shown promising results in some patients but remain under investigation. [40] [41] [42]

In the early months of the pandemic, many ICU doctors faced with the deadly nature of the virus ventured to prescribe conjectured treatments because of the unprecedented circumstances. [43] However, the standard of care for most intractable illnesses is that, as it develops over years, doctors build a body of research that tests various theories, compares and contrasts dosages, and measures one drug’s power against another. [43]

Several antiviral drugs are under investigation for COVID-19, though none has yet been shown to be clearly effective on mortality in published randomized controlled trials. [44] Convalescent plasma, plasma from persons who have recovered from SARS-CoV-2 infection, as a treatment option was frequently implemented during 2020, with preliminary reports at the time indicating that it was well tolerated and with low risk of adverse events. [45] Convalescent plasma even received Emergency Use Authorization in the US in August 2020. Further trial studies found convalescent plasma to be ineffective. [46] [47] Other trials are investigating whether existing medications can be used effectively against the body's immune reaction to SARS-CoV-2 infection. [44] [48] Research into potential treatments started in January 2020, [49] and several antiviral drugs are in clinical trials. [50] [51] Although new medications may take until 2021 to develop, [52] several of the medications being tested are already approved for other uses or are already in advanced testing. [53] Antiviral medication may be tried in people with severe disease. [4] The WHO recommended volunteers take part in trials of the effectiveness and safety of potential treatments. [54]

The monoclonal antibody therapies bamlanivimab/etesevimab and casirivimab/imdevimab have been found to reduce the number of hospitalizations, emergency room visits, and deaths. [55] [56] Both combination drugs have emergency use authorization by the US Food and Drug Administration (FDA). [55] [56]

Taking over-the-counter drugs such as paracetamol or ibuprofen, drinking fluids, and resting may help alleviate symptoms. [2] [57] [58] Depending on the severity, oxygen therapy and intravenous fluids may be required. [59]

Several potentially disease-modifying treatments have been investigated and found to be ineffective or unsafe, and are thus not recommended for use; these include baloxavir marboxil, lopinavir/ritonavir, ruxolitinib, chloroquine, hydroxychloroquine, interferon β-1a, and colchicine. [14] Favipiravir and nafamostat have shown mixed results but are still in clinical trials in some countries. [60] [61] [62]

Respiratory support

A critically ill patient receiving invasive ventilation in the intensive care unit of the Heart Institute, University of Sao Paulo, during the COVID-19 pandemic in Brazil. Due to a shortage of mechanical ventilators, a bridge ventilator is being used to automatically actuate a bag valve mask. Respiradores da USP utilizados do Incor (50119127303).jpg
A critically ill patient receiving invasive ventilation in the intensive care unit of the Heart Institute, University of São Paulo, during the COVID-19 pandemic in Brazil. Due to a shortage of mechanical ventilators, a bridge ventilator is being used to automatically actuate a bag valve mask.

Mechanical ventilation

Most cases of COVID‑19 are not severe enough to require mechanical ventilation or alternatives, but a percentage of cases are. [63] [64] The type of respiratory support for individuals with COVID‑19 related respiratory failure is being actively studied for people in the hospital, with some evidence that intubation can be avoided with a high flow nasal cannula or bi-level positive airway pressure. [65] Whether either of these two leads to the same benefit for people who are critically ill is not known. [66] Some doctors prefer staying with invasive mechanical ventilation when available because this technique limits the spread of aerosol particles compared to a high flow nasal cannula. [63]

Mechanical ventilation had been performed in 79% of critically ill people in hospital including 62% who previously received other treatment. Of these 41% died, according to one study in the United States. [67]

Severe cases are most common in older adults (those older than 60 years, [63] and especially those older than 80 years). [68] Many developed countries do not have enough hospital beds per capita, which limits a health system's capacity to handle a sudden spike in the number of COVID‑19 cases severe enough to require hospitalisation. [69] This limited capacity is a significant driver behind calls to flatten the curve. [69] One study in China found 5% were admitted to intensive care units, 2.3% needed mechanical support of ventilation, and 1.4% died. [16] In China, approximately 30% of people in hospital with COVID‑19 are eventually admitted to ICU. [70]

The administration of inhaled nitric oxide to people being ventilated is not recommended, and evidence around this practice is weak. [71]

Acute respiratory distress syndrome

Mechanical ventilation becomes more complex as acute respiratory distress syndrome (ARDS) develops in COVID‑19 and oxygenation becomes increasingly difficult. [72] Ventilators capable of pressure control modes and high PEEP [73] are needed to maximise oxygen delivery while minimising the risk of ventilator-associated lung injury and pneumothorax. [74]

Extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) is an artificial lung technology that has been used since the 1980s to treat respiratory failure and acute respiratory distress syndrome when conventional mechanical ventilation fails. In this complex procedure, blood is removed from the body via large cannulae, moved through a membrane oxygenator that performs the lung functions of oxygen delivery and carbon dioxide removal, and then returned to the body. The Extracorporeal Life Support Organization (ELSO) maintains a registry of outcomes for this technology, and it has been used in >120,000 patients over 435 ECMO centers worldwide with 40% mortality for adult respiratory patients. [75]

Initial use of ECMO in COVID-19 patients from China early in the pandemic suggested poor outcomes, with >90% mortality. [76] In March 2020, the ELSO registry began collecting data on the worldwide use of ECMO for patients with COVID-19 and reporting this data on the ELSO website in real time. In September 2020, the outcomes of 1,035 COVID-19 patients supported with ECMO from 213 experienced centers in 36 different countries were published in The Lancet, and demonstrated 38% mortality, which is similar to many other respiratory diseases treated with ECMO. The mortality is also similar to the 35% mortality seen in the EOLIA trial, the largest randomized controlled trial for ECMO in ARDS. [77] This registry based, multi-center, multi-country data provide provisional support for the use of ECMO for COVID-19 associated acute hypoxemic respiratory failure. Given that this is a complex technology that can be resource intense, guidelines exist for the use of ECMO during the COVID-19 pandemic. [78] [79] [80]

Prevention of onward transmission

The U.S. Centers for Disease Control and Prevention (CDC) recommends four steps to putting on PPE. DonningCDC2020.jpg
The U.S. Centers for Disease Control and Prevention (CDC) recommends four steps to putting on PPE.

Self-isolation has been recommended for people with mild cases of COVID-19 or who suspect they have been infected, even those with nonspecific symptoms, to prevent onward transmission of the virus and help reduce the burden on health care facilities. [2] In many jurisdictions, such as the United Kingdom, this is required by law. [82] Guidelines on self-isolation vary by country; the U.S. CDC and UK National Health Service have issued specific instructions, as have other local authorities. [83] [82]

Adequate ventilation, cleaning and disinfection, and waste disposal are also essential to prevent further spread of infection. [57]

Personal protective equipment

Precautions must be taken to minimise the risk of virus transmission, especially in healthcare settings when performing procedures that can generate aerosols, such as intubation or hand ventilation. [84] For healthcare professionals caring for people with COVID‑19, the CDC recommends placing the person in an Airborne Infection Isolation Room (AIIR) in addition to using standard precautions, contact precautions, and airborne precautions. [85]

The CDC outlines the guidelines for the use of personal protective equipment (PPE) during the pandemic. The recommended gear is a PPE gown, respirator or facemask, eye protection, and medical gloves. [86] [87]

When available, respirators (instead of face masks) are preferred. [88] CDC recommends mask use in public places, when not able to social distance, and while interacting with people outside of those that the person lives with. [89] N95 respirators are approved for industrial settings but the FDA has authorized the masks for use under an emergency use authorization (EUA). They are designed to protect from airborne particles like dust but effectiveness against a specific biological agent is not guaranteed for off-label uses. [90] When masks are not available, the CDC recommends using face shields or, as a last resort, homemade masks. [91]

Psychological support

Individuals may experience distress from quarantine, travel restrictions, side effects of treatment, or fear of the infection itself. To address these concerns, the National Health Commission of China published a national guideline for psychological crisis intervention on 27 January 2020. [92] [93]

The Lancet published a 14-page call for action focusing on the UK and stated conditions were such that a range of mental health issues was likely to become more common. BBC quoted Rory O'Connor in saying, "Increased social isolation, loneliness, health anxiety, stress, and an economic downturn are a perfect storm to harm people's mental health and wellbeing." [94] [95]

Special populations

Concurrent treatment of other conditions

Early in the pandemic, theoretical concerns were raised about ACE inhibitors and angiotensin receptor blockers. However, later research found no evidence to justify stopping these medications in people who take them for conditions such as high blood pressure. [15] [96] [97] [98] One study from 22 April found that people with COVID‑19 and hypertension had lower all-cause mortality when on these medications. [99] Similar concerns were raised about non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen; these were likewise not borne out, and NSAIDs may both be used to relieve symptoms of COVID-19 and continue to be used by people who take them for other conditions. [100]

People who use topical or systemic corticosteroids for respiratory conditions such as asthma or chronic obstructive pulmonary disease should continue taking them as prescribed even if they contract COVID-19. [37]

During pregnancy

To date, most SARS-CoV-2-related clinical trials have excluded, or included only a few, pregnant or lactating women. This limitation makes it difficult to make evidence-based therapy recommendations in these patients and potentially limits their COVID-19 treatment options. The US CDC recommends shared decision-making between the patient and the clinical team when treating pregnant women with investigational medication. [101]

Related Research Articles

Extracorporeal membrane oxygenation Technique of providing both cardiac and respiratory support

Extracorporeal membrane oxygenation (ECMO), also known as extracorporeal life support (ECLS), is an extracorporeal technique of providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequate amount of gas exchange or perfusion to sustain life. The technology for ECMO is largely derived from cardiopulmonary bypass, which provides shorter-term support with arrested native circulation. The device used is a membrane oxygenator, also known as an artificial lung.

Oseltamivir antiviral medication used against influenza A and influenza B

Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B (flu). Many medical organizations recommend it in people who have complications or are at high risk of complications within 48 hours of first symptoms of infection. They recommend it to prevent infection in those at high risk, but not the general population. The Centers for Disease Control and Prevention (CDC) recommends that clinicians use their discretion to treat those at lower risk who present within 48 hours of first symptoms of infection. It is taken by mouth, either as a pill or liquid.

Ivermectin Medication for parasite infestations

Ivermectin is a medication used to treat parasite infestations. In humans, these include head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis, and lymphatic filariasis. In veterinary medicine, the medication is used to prevent and treat heartworm and acariasis, among other indications. Ivermectin works through many mechanisms of action that result in the death of the targeted parasites; it can be taken by mouth or applied to the skin for external infestations. The drug belongs to the avermectin family of medications.

Chloroquine Medication used to treat malaria

Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication. Chloroquine is also occasionally used for amebiasis that is occurring outside the intestines, rheumatoid arthritis, and lupus erythematosus. While it has not been formally studied in pregnancy, it appears safe. It was studied to treat COVID-19 early in the pandemic, but these studies were largely halted in the summer of 2020, and is not recommended for this purpose. It is taken by mouth.

Hydroxychloroquine Antimalarial medication

Hydroxychloroquine, sold under the brand name Plaquenil among others, is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda. It is taken by mouth, often in the form of hydroxychloroquine sulfate.

Bronchoalveolar lavage (BAL) is a diagnostic method of the lower respiratory system in which a bronchoscope is passed through the mouth or nose into an appropriate airway in the lungs, with a measured amount of fluid introduced and then collected for examination. This method is typically performed to diagnose pathogenic infections of the lower respiratory airways, though it also has been shown to have utility in diagnosing interstitial lung disease. Bronchoalveolar lavage can be a more sensitive method of detection than nasal swabs in respiratory molecular diagnostics, as has been the case with SARS-CoV-2 where bronchoalveolar lavage samples detect copies of viral RNA after negative nasal swab testing.

Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis, a severe form of arthritis in children. It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.

Baricitinib

Baricitinib, sold under the brand name Olumiant among others, is a drug for the treatment of rheumatoid arthritis (RA) in adults whose disease was not well controlled by tumor necrosis factor (TNF) inhibitors. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2. The drug is approved for medical use in the European Union and in the United States.An important side effect of JAK inhibitors is serious bacterial, mycobacterial, fungal and viral infections.

Remdesivir Antiviral drug

Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein. During the COVID-19 pandemic, remdesivir was approved or authorized for emergency use to treat COVID‑19 in around 50 countries. Updated guidelines from the World Health Organization in November 2020 include a conditional recommendation against the use of remdesivir for the treatment of COVID-19.

Vaping-associated pulmonary injury (VAPI) also known as vaping-associated lung injury (VALI) or e-cigarette, or vaping, product use associated lung injury (E/VALI), is an umbrella term, used to describe lung diseases associated with the use of vaping products that can be severe and life-threatening. Symptoms can initially mimic common pulmonary diagnoses, such as pneumonia, but sufferers typically do not respond to antibiotic therapy. Differential diagnoses have overlapping features with VAPI, including COVID-19.

COVID-19 Contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, leading to an ongoing pandemic.

COVID-19 drug repurposing research Drug repurposing research related to COVID-19

Drug repositioning is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed. This is one line of scientific research which is being pursued to develop safe and effective COVID-19 treatments. Other research directions include the development of a COVID-19 vaccine and convalescent plasma transfusion.

COVID-19 drug development Preventative and therapeutic medications for COVID-19 infection

COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research, with 419 potential COVID-19 drugs in clinical trials, as of April 2021.

Solidarity trial Accelerated multinational clinical trial program to identify therapies against COVID-19

The Solidarity trial for treatments is a multinational Phase III-IV clinical trial organized by the World Health Organization (WHO) and partners to compare four untested treatments for hospitalized people with severe COVID-19 illness. The trial was announced 18 March 2020, and as of 6 August 2021, 12,000 patients in 30 countries had been recruited to participate in the trial.

Carolyn S. Calfee is a Professor of Medicine and Anaesthesia at the University of California, San Francisco. She works in intensive care at the UCSF Medical Center where she specialises in acute respiratory distress syndrome. During the COVID-19 pandemic Calfee studied why SARS-CoV-2 patients experienced such different symptoms.

Symptoms of COVID-19 Overview of the symptoms of COVID-19

Symptoms of COVID-19 are variable, ranging from mild symptoms to severe illness. Common symptoms include headache, loss of smell and taste, nasal congestion and runny nose, cough, muscle pain, sore throat, fever, diarrhea, and breathing difficulties. People with the same infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: one respiratory symptom cluster with cough, sputum, shortness of breath, and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhea. In people without prior ear, nose, and throat disorders, loss of taste combined with loss of smell is associated with COVID-19 and is reported in as many as 88% of cases

Impact of the COVID-19 pandemic on other health issues Health consequences of outbreak beyond the COVID-19 disease itself

The COVID-19 pandemic has had many impacts on global health beyond those caused by the COVID-19 disease itself. It has led to a reduction in hospital visits for other reasons. There have been 38 per cent fewer hospital visits for heart attack symptoms in the United States and 40 per cent fewer in Spain. The head of cardiology at the University of Arizona said, "My worry is some of these people are dying at home because they're too scared to go to the hospital." There is also concern that people with strokes and appendicitis are not seeking timely treatment. Shortages of medical supplies have impacted people with various conditions.

RECOVERY Trial Test of existing medicines on COVID-19

The Randomised Evaluation of COVID-19 Therapy is a large-enrollment clinical trial of possible treatments for people in the United Kingdom admitted to hospital with severe COVID-19 infection. The trial was later expanded to Indonesia, Nepal and Vietnam. The trial has tested ten interventions on adults: eight repurposed drugs, one newly developed drug and convalescent plasma.

Transmission of COVID-19 Mechanisms that spread coronavirus disease 2019

The transmission of COVID-19 is the passing of coronavirus disease 2019 from person to person. The disease is mainly transmitted via the respiratory route when people inhale droplets and small airborne particles that infected people exhale as they breathe, talk, cough, sneeze, or sing. Infected people are more likely to transmit COVID-19 when they are physically close. However, infection can occur over longer distances, particularly indoors.

Chloroquine and hydroxychloroquine during the COVID-19 pandemic

Chloroquine and hydroxychloroquine are anti-malarial medications also used against some auto-immune diseases. Chloroquine, along with hydroxychloroquine, was an early experimental treatment for COVID-19. They are very effective for preventing infection.

References

  1. 1 2 3 4 5 Siemieniuk RA, Bartoszko JJ, Ge L, Zeraatkar D, Izcovich A, Kum E, et al. (July 2020). "Drug treatments for covid-19: living systematic review and network meta-analysis". BMJ. 370: m2980. doi: 10.1136/bmj.m2980 . PMC   7390912 . PMID   32732190.
  2. 1 2 3 4 "Coronavirus". WebMD. Archived from the original on 2020-02-01. Retrieved 2020-02-01.
  3. Tao K, Tzou PL, Nouhin J, Bonilla H, Jagannathan P, Shafer RW (July 2021). "SARS-CoV-2 Antiviral Therapy". Clinical Microbiology Reviews: e0010921. doi:10.1128/CMR.00109-21. PMC   8404831 . PMID   34319150. S2CID   236472654.
  4. 1 2 Fisher D, Heymann D (February 2020). "Q&A: The novel coronavirus outbreak causing COVID-19". BMC Medicine. 18 (1): 57. doi: 10.1186/s12916-020-01533-w . PMC   7047369 . PMID   32106852.
  5. Liu K, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, et al. (May 2020). "Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province". Chinese Medical Journal. 133 (9): 1025–1031. doi: 10.1097/CM9.0000000000000744 . PMC   7147277 . PMID   32044814.
  6. Wang T, Du Z, Zhu F, Cao Z, An Y, Gao Y, Jiang B (March 2020). "Comorbidities and multi-organ injuries in the treatment of COVID-19". Lancet. Elsevier BV. 395 (10228): e52. doi: 10.1016/s0140-6736(20)30558-4 . PMC   7270177 . PMID   32171074.
  7. Wang Y, Wang Y, Chen Y, Qin Q (March 2020). "Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures". Journal of Medical Virology. 92 (6): 568–576. doi: 10.1002/jmv.25748 . PMC   7228347 . PMID   32134116.
  8. Martel J, Ko YF, Young JD, Ojcius DM (May 2020). "Could nasal breathing help to mitigate the severity of COVID-19". Microbes and Infection. 22 (4–5): 168–171. doi:10.1016/j.micinf.2020.05.002. PMC   7200356 . PMID   32387333.
  9. "Coronavirus recovery: breathing exercises". www.hopkinsmedicine.org. Johns Hopkins Medicine. Retrieved 30 July 2020.
  10. Wang L, Wang Y, Ye D, Liu Q (March 2020). "Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence". International Journal of Antimicrobial Agents. 55 (6): 105948. doi:10.1016/j.ijantimicag.2020.105948. PMC   7156162 . PMID   32201353.
  11. U.S. Centers for Disease Control and Prevention (5 April 2020). "What to Do if You Are Sick". Centers for Disease Control and Prevention (CDC). Archived from the original on 14 February 2020. Retrieved 24 April 2020.
  12. "Update to living WHO guideline on drugs for covid-19". BMJ (Clinical Research Ed.). 371: m4475. November 2020. doi: 10.1136/bmj.m4475 . ISSN   1756-1833. PMID   33214213. S2CID   227059995.
  13. "Q&A: Dexamethasone and COVID-19". World Health Organization (WHO). Retrieved 2020-07-11.
  14. 1 2 "Home". National COVID-19 Clinical Evidence Taskforce. Retrieved 2020-07-11.
  15. 1 2 3 4 "COVID-19 Treatment Guidelines". www.nih.gov. National Institutes of Health. Retrieved 2021-01-18.
  16. 1 2 Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. (April 2020). "Clinical Characteristics of Coronavirus Disease 2019 in China". The New England Journal of Medicine. Massachusetts Medical Society. 382 (18): 1708–1720. doi: 10.1056/nejmoa2002032 . PMC   7092819 . PMID   32109013.
  17. Henry BM (April 2020). "COVID-19, ECMO, and lymphopenia: a word of caution". The Lancet. Respiratory Medicine. Elsevier BV. 8 (4): e24. doi:10.1016/s2213-2600(20)30119-3. PMC   7118650 . PMID   32178774.
  18. Kim JS, Lee JY, Yang JW, Lee KH, Effenberger M, Szpirt W, et al. (2021). "Immunopathogenesis and treatment of cytokine storm in COVID-19". Theranostics. 11 (1): 316–329. doi:10.7150/thno.49713. PMC   7681075 . PMID   33391477.
  19. May Sidik, Saima (2 November 2021). "Common Antidepressant Slashes Risk of COVID Death". Nature. Retrieved 8 November 2021.
  20. Aripaka, Pushkala (5 November 2021). "Britain approves Merck's COVID-19 pill in world first". Reuters. Retrieved 8 November 2021.
  21. Beasley, Deena (5 November 2021). "Pfizer says its antiviral pill slashes risk of severe COVID-19 by 89%". Reuters. Retrieved 8 November 2021.
  22. 1 2 Kim PS, Read SW, Fauci AS (December 2020). "Therapy for Early COVID-19: A Critical Need". JAMA. American Medical Association (AMA). 324 (21): 2149–2150. doi: 10.1001/jama.2020.22813 . PMID   33175121.
  23. 1 2 3 "COVID-19 Treatment Guidelines". www.nih.gov. National Institutes of Health. Retrieved 2021-01-18./
  24. Hsu J (November 2020). "Covid-19: What now for remdesivir?". BMJ. 371: m4457. doi: 10.1136/bmj.m4457 . PMID   33214186.
  25. Molnupiravir: First pill to treat Covid gets approval in UK Jim Reed, 4 November 2021 www.bbc.co.uk, accessed 23 November 2021
  26. "Clinical management of COVID-19". World Health Organization (WHO). 2020-05-27. Retrieved 2021-01-18.
  27. "Coronavirus (COVID-19) | NICE". National Institute for Health and Care Excellence. Retrieved 2021-01-18.
  28. Cheng ZJ, Shan J (April 2020). "2019 Novel coronavirus: where we are and what we know". Infection. 48 (2): 155–163. doi: 10.1007/s15010-020-01401-y . PMC   7095345 . PMID   32072569.
  29. Farkas J (March 2020). COVID-19—The Internet Book of Critical Care (digital) (Reference manual). USA: EMCrit. Archived from the original on 11 March 2020. Retrieved 13 March 2020.
  30. "COVID19—Resources for Health Care Professionals". Penn Libraries. 11 March 2020. Archived from the original on 14 March 2020. Retrieved 13 March 2020.
  31. Guo W, Pan B, Sakkiah S, Ji Z, Yavas G, Lu Y, et al. (July 2021). "Informing selection of drugs for COVID-19 treatment through adverse events analysis". Scientific Reports. 11 (1): 14022. doi:10.1038/s41598-021-93500-5. PMC   8263777 . PMID   34234253.
  32. Zimmer, Carl; Wu, Katherine J.; Corum, Jonathan (16 July 2020). "Coronavirus Drug and Treatment Tracker". The New York Times. New York Times.
  33. "COVID-19 Frequently Asked Questions: Drugs (Medicines)". U.S. Food and Drug Administration. 2021-02-19. Retrieved 2021-02-20.
  34. "Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Monoclonal Antibody Bamlanivimab". U.S. Food and Drug Administration (FDA) (Press release). 16 April 2021. Retrieved 16 April 2021.PD-icon.svgThis article incorporates text from this source, which is in the public domain .
  35. "Treatments and vaccines for COVID-19: authorised medicines". European Medicines Agency. Retrieved 2021-02-20.
  36. Turkia, Mika (31 December 2020). "The History of Methylprednisolone, Ascorbic Acid, Thiamine, and Heparin Protocol and I-MASK+ Ivermectin Protocol for COVID-19". Cureus. doi:10.7759/cureus.12403.
  37. 1 2 "Australian guidelines for the clinical care of people with COVID-19". National COVID-19 Clinical Evidence Taskforce. National COVID-19 Clinical Evidence Taskforce. Retrieved 11 July 2020.
  38. Rizk JG, Kalantar-Zadeh K, Mehra MR, Lavie CJ, Rizk Y, Forthal DN (September 2020). "Pharmaco-Immunomodulatory Therapy in COVID-19". Drugs. Springer. 80 (13): 1267–1292. doi: 10.1007/s40265-020-01367-z . PMC   7372203 . PMID   32696108.
  39. Wagner, Carina; Griesel, Mirko; Mikolajewska, Agata; Mueller, Anika; Nothacker, Monika; Kley, Karoline; Metzendorf, Maria-Inti; Fischer, Anna-Lena; Kopp, Marco; Stegemann, Miriam; Skoetz, Nicole; Fichtner, Falk (16 August 2021). "Systemic corticosteroids for the treatment of COVID-19". Cochrane Database of Systematic Reviews. 2021 (8). doi:10.1002/14651858.CD014963.
  40. Frohman EM, Villemarette-Pittman NR, Rodriguez A, Glanzman R, Rugheimer S, Komogortsev O, et al. (July 2021). "Application of an evidence-based, out-patient treatment strategy for COVID-19: Multidisciplinary medical practice principles to prevent severe disease". Journal of the Neurological Sciences. 426: 117463. doi:10.1016/j.jns.2021.117463. PMC   8055502 . PMID   33971376.
  41. Viswanatha GL, Anjana Male CK, Shylaja H (July 2021). "Efficacy and safety of tocilizumab in the management of COVID-19: a systematic review and meta-analysis of observational studies". Clinical and Experimental Rheumatology. PMID   34251307.
  42. Shang L, Lye DC, Cao B (August 2021). "Contemporary narrative review of treatment options for COVID-19". Respirology. 26 (8): 745–767. doi: 10.1111/resp.14106 . PMC   8446994 . PMID   34240518.
  43. 1 2 Dominus S (5 August 2020). "The Covid Drug Wars That Pitted Doctor vs. Doctor". The New York Times.
  44. 1 2 Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB (May 2020). "Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review". JAMA. 323 (18): 1824–1836. doi: 10.1001/jama.2020.6019 . PMID   32282022. S2CID   215752785.
  45. Janiaud, Perrine; Axfors, Cathrine; Schmitt, Andreas M.; Gloy, Viktoria; Ebrahimi, Fahim; Hepprich, Matthias; Smith, Emily R.; Haber, Noah A.; Khanna, Nina; Moher, David; Goodman, Steven N.; Ioannidis, John P. A.; Hemkens, Lars G. (23 March 2021). "Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis". JAMA. 325 (12): 1185. doi:10.1001/jama.2021.2747.
  46. Piechotta V, Iannizzi C, Chai KL, Valk SJ, Kimber C, Dorando E, et al. (May 2021). "Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review". The Cochrane Database of Systematic Reviews. 2021 (5): CD013600. doi:10.1002/14651858.CD013600.pub4. PMC  8135693. PMID   34013969.
  47. Abani, Obbina; et al. (RECOVERY Collaborative Group) (May 2021). "Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial". Lancet. 397 (10289): 2049–2059. doi: 10.1016/S0140-6736(21)00897-7 . PMC   8121538 . PMID   34000257.
  48. McCreary EK, Pogue JM (April 2020). "Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options". Open Forum Infectious Diseases. 7 (4): ofaa105. doi:10.1093/ofid/ofaa105. PMC   7144823 . PMID   32284951.
  49. "Chinese doctors using plasma therapy on coronavirus, WHO says 'very valid' approach". Reuters. 17 February 2020. Archived from the original on 4 March 2020. Retrieved 19 March 2020.
  50. Steenhuysen J, Kelland K (24 January 2020). "With Wuhan virus genetic code in hand, scientists begin work on a vaccine". Reuters . Archived from the original on 25 January 2020. Retrieved 25 January 2020.
  51. Duddu P (19 February 2020). "Coronavirus outbreak: Vaccines/drugs in the pipeline for Covid-19". clinicaltrialsarena.com. Archived from the original on 19 February 2020.
  52. Lu H (March 2020). "Drug treatment options for the 2019-new coronavirus (2019-nCoV)". Bioscience Trends. 14 (1): 69–71. doi: 10.5582/bst.2020.01020 . PMID   31996494.
  53. Li G, De Clercq E (March 2020). "Therapeutic options for the 2019 novel coronavirus (2019-nCoV)". Nature Reviews. Drug Discovery. 19 (3): 149–150. doi: 10.1038/d41573-020-00016-0 . PMID   32127666.
  54. Nebehay S, Kelland K, Liu R (5 February 2020). "WHO: 'no known effective' treatments for new coronavirus". Thomson Reuters. Archived from the original on 5 February 2020. Retrieved 5 February 2020.
  55. 1 2 "FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19". U.S. Food and Drug Administration (FDA) (Press release). 10 February 2021. Retrieved 9 February 2021.PD-icon.svgThis article incorporates text from this source, which is in the public domain .
  56. 1 2 "Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19". U.S. Food and Drug Administration (FDA). 23 November 2020. Retrieved 17 April 2021.PD-icon.svgThis article incorporates text from this source, which is in the public domain .
  57. 1 2 "Home care for patients with suspected or confirmed COVID-19 and management of their contacts" (PDF). World Health Organization (WHO). 2020-08-13. Retrieved 2021-01-18.
  58. "Prevention & Treatment". U.S. Centers for Disease Control and Prevention (CDC). 2020-02-15. Archived from the original on 2019-12-15. Retrieved 21 January 2020.PD-icon.svgThis article incorporates text from this source, which is in the public domain .
  59. "Overview of novel coronavirus (2019-nCoV)—Summary of relevant conditions". The BMJ . Archived from the original on 2020-01-31. Retrieved 2020-02-01.
  60. Janik E, Niemcewicz M, Podogrocki M, Saluk-Bijak J, Bijak M. Existing Drugs Considered as Promising in COVID-19 Therapy. Int J Mol Sci. 2021 May 21;22(11):5434. doi : 10.3390/ijms22115434 PMID   34063964
  61. Hall K, Mfone F, Shallcross M, Pathak V. Review of Pharmacotherapy Trialed for Management of the Coronavirus Disease-19. Eurasian J Med. 2021 Jun;53(2):137-143. doi : 10.5152/eurasianjmed.2021.20384 PMID   34177298
  62. Heustess AM, Allard MA, Thompson DK, Fasinu PS. Clinical Management of COVID-19: A Review of Pharmacological Treatment Options. Pharmaceuticals (Basel). 2021 May 28;14(6):520. doi : 10.3390/ph14060520 PMID   34071185
  63. 1 2 3 Murthy S, Gomersall CD, Fowler RA (March 2020). "Care for Critically Ill Patients With COVID-19". JAMA. 323 (15): 1499–1500. doi: 10.1001/jama.2020.3633 . PMID   32159735. Archived from the original on 18 March 2020. Retrieved 18 March 2020.
  64. "Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected" (PDF). World Health Organization (WHO). 28 January 2020. Archived (PDF) from the original on 26 February 2020. Retrieved 18 March 2020.
  65. Wang K, Zhao W, Li J, Shu W, Duan J (March 2020). "The experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of Chongqing, China". Annals of Intensive Care. 10 (1): 37. doi:10.1186/s13613-020-00653-z. PMC   7104710 . PMID   32232685.
  66. McEnery T, Gough C, Costello RW (April 2020). "COVID-19: Respiratory support outside the intensive care unit". The Lancet. Respiratory Medicine. 8 (6): 538–539. doi:10.1016/S2213-2600(20)30176-4. PMC   7146718 . PMID   32278367.
  67. Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, et al. (June 2020). "Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study". The Lancet. 395 (10239): 1763–70. doi: 10.1016/S0140-6736(20)31189-2 . PMC   7237188 . PMID   32442528.
  68. Ferguson NM, Laydon D, Nedjati-Gilani G, Imai N, Ainslie K, Baguelin M (16 March 2020). Report 9: Impact of non-pharmaceutical interventions (NPIs) to reduce COVID19 mortality and healthcare demand (Report). Imperial College London. Table 1. doi: 10.25561/77482 . hdl:20.1000/100. Archived from the original on 21 March 2020. Retrieved 25 March 2020.
  69. 1 2 Scott D (16 March 2020). "Coronavirus is exposing all of the weaknesses in the US health system High health care costs and low medical capacity made the US uniquely vulnerable to the coronavirus". Vox. Archived from the original on 18 March 2020. Retrieved 18 March 2020.
  70. "Interim Clinical Guidance for Management of Patients with Confirmed Coronavirus Disease (COVID-19)". Centers for Disease Control and Prevention (CDC). 6 April 2020. Archived from the original on 2 March 2020. Retrieved 19 April 2020.
  71. Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. (May 2020). "Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)". Intensive Care Med (Clinical practice guideline). 46 (5): 854–887. doi: 10.1007/s00134-020-06022-5 . PMC   7101866 . PMID   32222812.
  72. Matthay MA, Aldrich JM, Gotts JE (May 2020). "Treatment for severe acute respiratory distress syndrome from COVID-19". The Lancet. Respiratory Medicine. 8 (5): 433–434. doi:10.1016/S2213-2600(20)30127-2. PMC   7118607 . PMID   32203709.
  73. Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, et al. (March 2010). "Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis". JAMA. 303 (9): 865–73. doi: 10.1001/jama.2010.218 . PMID   20197533.
  74. Diaz R, Heller D (2020). Barotrauma And Mechanical Ventilation. StatPearls. StatPearls Publishing. PMID   31424810.
  75. "Extracorporeal Life Support Organization - ECMO and ECLS > Registry > Statistics > International Summary". www.elso.org. Retrieved 2020-09-28.
  76. Henry BM, Lippi G (August 2020). "Poor survival with extracorporeal membrane oxygenation in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19): Pooled analysis of early reports". Journal of Critical Care. 58: 27–8. doi:10.1016/j.jcrc.2020.03.011. PMC   7118619 . PMID   32279018.
  77. Combes A, Hajage D, Capellier G, Demoule A, Lavoué S, Guervilly C, et al. (May 2018). "Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome". New England Journal of Medicine. 378 (21): 1965–75. doi: 10.1056/NEJMoa1800385 . PMID   29791822. S2CID   44106489.
  78. Bartlett RH, Ogino MT, Brodie D, McMullan DM, Lorusso R, MacLaren G, et al. (May 2020). "Initial ELSO Guidance Document: ECMO for COVID-19 Patients with Severe Cardiopulmonary Failure". ASAIO Journal. 66 (5): 472–4. doi:10.1097/MAT.0000000000001173. PMC   7273858 . PMID   32243267.
  79. Shekar K, Badulak J, Peek G, Boeken U, Dalton HJ, Arora L, et al. (July 2020). "Extracorporeal Life Support Organization Coronavirus Disease 2019 Interim Guidelines: A Consensus Document from an International Group of Interdisciplinary Extracorporeal Membrane Oxygenation Providers". ASAIO Journal. 66 (7): 707–21. doi:10.1097/MAT.0000000000001193. PMC   7228451 . PMID   32358233.
  80. Ramanathan K, Antognini D, Combes A, Paden M, Zakhary B, Ogino M, et al. (May 2020). "Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases". The Lancet Respiratory Medicine. 8 (5): 518–26. doi:10.1016/s2213-2600(20)30121-1. PMC   7102637 . PMID   32203711.
  81. "Sequence for Putting On Personal Protective Equipment (PPE)" (PDF). Centers for Disease Control and Prevention (CDC). Archived (PDF) from the original on 5 March 2020. Retrieved 8 March 2020.
  82. 1 2 "When to self-isolate and what to do - Coronavirus (COVID-19)". NHS. 2021-01-08. Retrieved 2021-01-18.
  83. U.S. Centers for Disease Control and Prevention (2021-01-07). "Isolate If You Are Sick". CDC. Retrieved 2021-01-18.
  84. Cheung JC, Ho LT, Cheng JV, Cham EY, Lam KN (April 2020). "Staff safety during emergency airway management for COVID-19 in Hong Kong". The Lancet. Respiratory Medicine. 8 (4): e19. doi: 10.1016/s2213-2600(20)30084-9 . PMC   7128208 . PMID   32105633.
  85. "What healthcare personnel should know about caring for patients with confirmed or possible coronavirus disease 2" (PDF). Centers for Disease Control and Prevention (CDC). 12 March 2020. Retrieved 31 March 2020.
  86. "Coronavirus Disease 2019 (COVID-19)". Centers for Disease Control and Prevention (CDC). 11 February 2020. Archived from the original on 4 March 2020. Retrieved 11 March 2020.
  87. "Coronavirus Disease 2019 (COVID-19)". Centers for Disease Control and Prevention (CDC). 11 February 2020. Archived from the original on 4 March 2020. Retrieved 8 March 2020.
  88. "Interim Infection Prevention and Control Recommendations for Patients with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19) in Healthcare Settings". Centers for Disease Control and Prevention (CDC). 11 February 2020. Archived from the original on 4 March 2020. Retrieved 25 March 2020.
  89. CDC (2020-02-11). "Coronavirus Disease 2019 (COVID-19)". Centers for Disease Control and Prevention. Retrieved 2020-07-30.
  90. "Coronavirus Disease 2019 (COVID-19) Frequently Asked Questions". Food and Drug Administration.
  91. "Strategies for Optimizing the Supply of Facemasks". Centers for Disease Control and Prevention (CDC). 11 February 2020. Archived from the original on 23 March 2020. Retrieved 23 March 2020.
  92. Xiang YT, Yang Y, Li W, Zhang L, Zhang Q, Cheung T, Ng CH (March 2020). "Timely mental health care for the 2019 novel coronavirus outbreak is urgently needed". The Lancet. Psychiatry. 7 (3): 228–229. doi: 10.1016/S2215-0366(20)30046-8 . PMC   7128153 . PMID   32032543.
  93. Kang L, Li Y, Hu S, Chen M, Yang C, Yang BX, et al. (March 2020). "The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus". The Lancet. Psychiatry. 7 (3): e14. doi: 10.1016/S2215-0366(20)30047-X . PMC   7129673 . PMID   32035030.
  94. Coronavirus: 'Profound' mental health impact prompts calls for urgent research, BBC, Philippa Roxby, 16 April 2020.
  95. Multidisciplinary research priorities for the COVID‑19 pandemic: a call for action for mental health science, The Lancet, Emily Holmes, Rory O'Connor, Hugh Perry, et al., 15 April 2020, page 1: "A fragmented research response, characterised by small-scale and localised initiatives, will not yield the clear insights necessary to guide policymakers or the public."
  96. "Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician". Archived from the original on 21 March 2020. Retrieved 21 March 2020.
  97. "Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician". American Heart Association (Press release). 17 March 2020. Archived from the original on 24 March 2020. Retrieved 25 March 2020.
  98. de Simone G. "Position Statement of the ESC Council on Hypertension on ACE-Inhibitors and Angiotensin Receptor Blockers". Council on Hypertension of the European Society of Cardiology. Archived from the original on 24 March 2020. Retrieved 24 March 2020.
  99. "New Evidence Concerning Safety of ACE Inhibitors, ARBs in COVID-19". Pharmacy Times. Retrieved 2 May 2020.
  100. "FDA advises patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19". U.S. Food and Drug Administration (FDA). 19 March 2020. Archived from the original on 27 March 2020. Retrieved 27 March 2020.
  101. "Coronavirus Disease 2019 (COVID-19) Treatment Guidelines" (PDF). CDC. Centers for Disease control and Prevention. Retrieved 12 November 2020.PD-icon.svgThis article incorporates text from this source, which is in the public domain .

Treatment guidelines