COVID-19 as of today (March 23-25; summary is my own, not my employer’s):

PREFACE: Today marks one month since I first started writing these updates. I usually try to keep emotion out of these, but I have had a very difficult time recently. It is hard to continue to speak calmly to those who don’t understand the gravity of the situation by now. It is extremely difficult that the most effective methods we currently have in our toolbox to fight this pandemic - aside from isolating known cases and quarantining their contacts - require massive displays of individual responsibility over an extended period of time. It is impossible to require people to stay home when they do not have enough money to buy food for themselves or their family and they are not protected from being thrown out onto the street for missing a single rent payment. I’ve been seriously grappling with what to include in this update over the past few days. I don’t intend on stopping them any time soon, so long as there is information out there that can help others. SO – to mark the first month, I decided that instead of focusing on news today, I want to shine a light on the clinical trials that are currently being done in the face of this disease. The amount of cooperation it takes to conduct these during such a time as this is truly astounding, and every healthcare worker, researcher and participant involved is an inspiration. Also, I tried my best to write what these clinical trials are testing in layman’s terms, but I know some of it may still be difficult to wrap your head around. Please tell me if there’s anything you’d like further clarification on, and I’d be more than happy to provide it.

[NOTE: You can find definitions of some terms I use commonly in these posts, as well as the link to your state health department’s up-to-date COVID-19 case counts, here (I updated several links today for health departments that recently changed where they were reporting their numbers): https://docs.google.com/document/d/1CQZ9KGRJ8gLqSs89sEjpVSr5jBEkgvgBT-QoMOy-O0w]

Countries and Territories with New Cases, Extent of Pandemic:

Countries Belize, Laos, Libya, Myanmar, and territory Turks and Caicos each report their first COVID-19 cases. The virus is now present in 169 countries and 27 territories. Roughly 97.6% of the world’s population now lives in a country or territory with active cases. [1-4]

Drug Clinical Trials:

Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain, Switzerland and Thailand are all enrolled in the World Health Organization's SOLIDARITY Trial, which is testing four drugs – remdesivir (an HIV drug); a combination of two drugs, lopinavir and ritonavir; the two drugs plus interferon beta; and hydroxychloroquine – and will compare their effectiveness to what is called standard of care (the regular support hospitals treating COVID-19 patients use now). When a person with a confirmed case of COVID-19 is deemed eligible, the physician can enter the patient’s data into a WHO website, including any underlying condition that could change the course of the disease, such as diabetes or HIV infection. The participant has to sign an informed consent form that is scanned and sent to WHO electronically. After the physician states which drugs are available at his or her hospital, the website will randomize the patient to one of the drugs available or to the local standard care for COVID-19. [5, 6]

Three studies are currently testing the efficacy of tocilizumab, an immunosuppressant mainly used for the treatment of rheumatoid arthritis (RA) and systemic juvenile idiopathic arthritis, in COVID-19 patients who have developed pneumonia. The primary outcome measure being tested at 27 locations in Italy is whether or not patients die within one month after receiving treatment; this study is actively recruiting 330 participants. The primary outcome measure at a study being conducted in Ancona, Italy, is the level of patients' pulmonary function over a 7-day period. The primary outcome measure in a US study (that has not yet published study locations or started recruiting) is the patient's clinical status over a 4-week period. A fourth study actively recruiting 150 participants at 8 locations in Wuhan, 2 in Beijing, and 1 in Hefei, China, is testing the combination of tocilizumab and favipiravir, a new antiviral drug developed in Japan; this study does not appear to be limited to COVID-19 patients with pneumonia. Its primary outcome measure is whether or not the patients have been cured. A fifth study being conducted in Wuhan is comparing the effectiveness of tocilizumab to continuous renal replacement therapy (dialysis conducted throughout the duration of the illness); its primary outcome measures are fever and oxygen saturation levels. [7-11]

New York is recruiting COVID-19 patients to test the efficacy of sarilumab, a drug currently used for the treatment of rheumatoid arthritis, in severe or critical cases. The primary outcome measures being tested are whether fever decreases in 48 hours (without fever-reducing medications) and the severity of a case 15 days after treatment. The study is currently recruiting and will include 400 participants. [12]

A hospital in Hubei, China is recruiting patients to test the efficacy of sildenafil, a drug currently used to treat erectile dysfunction and high blood pressure in the lungs (pulmonary arterial hypertension), in COVID-19 patients. The primary outcome measures being tested are whether a patient enters a stage of critical illness (how quickly and for how long), and how quickly the patient's symptoms resolve. The study is currently recruiting and will include 10 participants. [13]

A clinical trial in Pozzili, Italy is underway to determine the effects of angiotensin receptor-blocker (ARB) or ACE inhibitor (ACE-I) drugs on COVID-19 patients. The specific drugs to be tested are not yet listed. The primary outcome measures being tested are development and severity of pneumonia or acute respiratory distress syndrome. This study is not yet recruiting. [14]

[TWO PARAGRAPHS] Nine clinical trials are underway to test the effectiveness of hydroxychloroquine. The primary outcome measure being studied in Akershus, Norway is patients' viral load four days after treatment. Another study in Norway is comparing hydroxychloroquine and remdesivir for treatment of hospitalized COVID-19 patients; its primary outcome measure is the rate of in-hospital death up to three weeks after treatment. Three studies being conducted by the University of Minnesota, Columbia University, and Mexico's National Institute of Respiratory Diseases (NIRD) are testing the effectiveness of the drug as post-exposure prophylaxis (that is, the drug is given after a person was exposed to a known case but before developing symptoms); each one's primary outcome measure is how many participants developed COVID-19 after treatment.

A study being conducted by Mexico's National Institute of Respiratory Diseases aims to test the drug's effectiveness on patients with severe illness; its primary outcome measure is all-cause mortality up to 120 days after treatment. A medical center in South Korea is testing the effectiveness of lopinavir/ritonavir and hydroxychloroquine in patients with mild symptoms of COVID-19. The primary outcome measure being tested is the patient's viral load on six different days since the patient was hospitalized. The study is currently recruiting and will include 150 participants. A study in Thailand is testing various combinations of hydroxychloroquine, protease inhibitors (drugs often used for HIV/AIDS treatment), oseltamivir (aka Tamiflu), and favipiravir on mild to critical COVID-19 patients; its primary outcome measure is the time it takes for the virus that causes COVID-19 to leave the body. The most recently announced clinical trial will be conducted at 22 study sites in Brazil; it aims to compare hydroxychloroquine with the combination of hydroxychloroquine and azithromycin in COVID-19 patients hospitalized with pneumonia. Its primary outcome measure is patients’ clinical statuses 15 days after treatment. [15-23]

A study with locations in California, Illinois, Massachusetts, Rhode Island, Washington State, Hong Kong, South Korea, Singapore and Taiwan is testing the effectiveness of two remdesivir regimens in treating COVID-19 patients. The primary outcome measures being tested are fever and oxygen saturation levels. The study is currently recruiting and will include 400 participants. [24]

A study in Shandong, China is testing the effectiveness of bevacizumab, a drug used to treat colorectal, lung, glioblastoma, kidney, cervical, and ovarian cancer, in severe and critically ill COVID-19 patients. The primary outcome being measured is patients' oxygen saturation levels by the 7th day after hospital admission. The study is currently recruiting and will include 118 participants. [25]

Two studies in Wenzhou, China are testing the effectiveness of thalidomide, a drug used for leprosy and multiple myeloma (but not to be used by pregnant women because it causes severe birth defects), in both moderate and severe COVID-19 patients. The primary outcome measure for both studies is the time to clinical improvement of symptoms. The studies are not yet recruiting. [26, 27]

Vaccine Clinical Trials:

At least four Phase 1 COVID-19 vaccine clinical trials are taking place. Phase 1 trials are where small groups of people receive the trial vaccine and its safety and ability to produce an immune response are measured. Vaccines are required to go through at least three phases of clinical trials, though many will go through four (see the CDC's webpage on vaccine testing for more details). The four Phase 1 clinical trials are being conducted in Atlanta, GA (not yet recruiting); Seattle, WA (recruiting); Wuhan, China (recruiting); and Shenzhen, China (3 locations - recruiting). [28-31]

Other Clinical Trials:

Two studies in Amman, Jordan and Campinas, Brazil are testing the effectiveness of mesenchymal stem cells in COVID-19 patients. The primary outcome measures being tested in Jordan are progression of symptoms, CT scans, and test results; in Brazil, the measure is changes in pneumonia status. The study in Jordan is currently recruiting and will include 5 participants. The study in Brazil is not yet recruiting. [32, 33]

A study at San Matteo Hospital in Italy is testing the effectiveness of hyperimmune plasma – essentially, blood from COVID-19 survivors who have high levels of antibodies after recovering – in critical COVID-19 patients. The primary outcome measure for this study is whether the patient died within 7 days of receiving this treatment. The study has recruited 49 patients and is currently active. [34]

[1] WHO COVID-19 Situation Report, 03-23-20

https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200323-sitrep-63-covid-19.pdf?sfvrsn=b617302d_4

[2] WHO COVID-19 Situation Report, 03-24-20

https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200324-sitrep-64-covid-19.pdf?sfvrsn=723b221e_2

[3] WHO COVID-19 Situation Report, 03-25-20

https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200325-sitrep-65-covid-19.pdf?sfvrsn=2b74edd8_2

[4] Countries in the World by Population

https://www.worldometers.info/world-population/population-by-country/

[5] Thailand joins the WHO “Solidarity Trial”: global testing of effective treatments of COVID-19 across 8 countries – an aggressive effort to save lives from the pandemic

https://www.who.int/thailand/news/detail/20-03-2020-thailand-joins-the-who-solidarity-trial-global-testing-of-effective-treatments-of-covid-19-across-8-countries-an-aggressive-effort-to-save-lives-from-the-pandemic

[6] WHO launches global megatrial of the four most promising coronavirus treatments

https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments

[7] Tocilizumab in COVID-19 Pneumonia (TOCIVID-19) (TOCIVID-19)

https://clinicaltrials.gov/ct2/show/NCT04317092

[8] A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients with Severe COVID-19 Pneumonia (COVACTA)

https://clinicaltrials.gov/ct2/show/NCT04320615

[9] Tocilizumab for SARS-CoV2 Severe Pneumonitis

https://clinicaltrials.gov/ct2/show/NCT04315480

[10] Favipiravir Combined with Tocilizumab in the Treatment of Corona Virus Disease 2019

https://clinicaltrials.gov/ct2/show/NCT04310228

[11] Tocilizumab vs CRRT in Management of Cytokine Release Syndrome (CRS) in COVID-19 (TACOS)

https://clinicaltrials.gov/ct2/show/NCT04306705

[12] Evaluation of the Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19

https://clinicaltrials.gov/ct2/show/NCT04315298

[13] A Pilot Study of Sildenafil in COVID-19

https://clinicaltrials.gov/ct2/show/NCT04304313

[14] ACE Inhibitors, Angiotensin II Type-I Receptor Blockers and Severity of COVID-19 (CODIV-ACE)

https://clinicaltrials.gov/ct2/show/NCT04318418

[15] Comparison of Lopinavir/Ritonavir or Hydroxychloroquine in Patients with Mild Coronavirus Disease (COVID-19)

https://clinicaltrials.gov/ct2/show/NCT04307693

[16] The Efficacy of Different Anti-viral Drugs in (Severe Acute Respiratory Syndrome-Corona Virus-2) SARS-CoV-2

https://clinicaltrials.gov/ct2/show/NCT04321616

[17] Norwegian Coronavirus Disease 2019 Study (NO COVID-19)

https://clinicaltrials.gov/ct2/show/NCT04316377

[18] Post-exposure Prophylaxis for SARS-Coronavirus-2

https://clinicaltrials.gov/ct2/show/NCT04308668

[19] Hydroxychloroquine Post Exposure Prophylaxis for Coronavirus Disease (COVID-19)

https://clinicaltrials.gov/ct2/show/NCT04318444

[20] Hydroxychloroquine Chemoprophylaxis in Healthcare Personnel in Contact With COVID-19 Patients (PHYDRA Trial) (PHYDRA)

https://clinicaltrials.gov/ct2/show/NCT04318015

[21] Hydroxychloroquine Treatment for Severe COVID-19 Pulmonary Infection (HYDRA Trial) (HYDRA)

https://clinicaltrials.gov/ct2/show/NCT04315896

[22] Various Combination of Protease Inhibitors, Oseltamivir, Favipiravir, and Hydroxychloroquine for Treatment of COVID19 : A Randomized Control Trial (THDMS-COVID19)

https://clinicaltrials.gov/ct2/show/NCT04303299

[23] Safety and Efficacy of Hydroxychloroquine Associated with Azithromycin in SARS-CoV2 Virus (Alliance Covid-19 Brasil II)

https://clinicaltrials.gov/ct2/show/NCT04321278

[24] Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants with Severe Coronavirus Disease (COVID-19)

https://clinicaltrials.gov/ct2/show/NCT04292899

[25] Bevacizumab in Severe or Critically Severe Patients With COVID-19 Pneumonia-RCT (BEST-RCT)

https://clinicaltrials.gov/ct2/show/NCT04305106

[26] The Efficacy and Safety of Thalidomide Combined with Low-dose Hormones in the Treatment of Severe COVID-19

https://clinicaltrials.gov/ct2/show/NCT04273581

[27] The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate New Coronavirus (COVID-19) Pneumonia

https://clinicaltrials.gov/ct2/show/NCT04273529

[28] Treatment of COVID-19 Patients Using Wharton's Jelly-Mesenchymal Stem Cells

https://clinicaltrials.gov/ct2/show/NCT04313322

[29] NestCell® Mesenchymal Stem Cell to Treat Patients with Severe COVID-19 Pneumonia (HOPE)

https://clinicaltrials.gov/ct2/show/NCT04315987

[30] Hyperimmune Plasma for Critical Patients With COVID-19 (COV19-PLASMA)

https://clinicaltrials.gov/ct2/show/NCT04321421

[31] Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) to Prevent SARS-CoV-2 Infection

https://clinicaltrials.gov/ct2/show/NCT04283461

[32] A Phase I Clinical Trial in 18-60 Adults (APICTH)

https://clinicaltrials.gov/ct2/show/NCT04313127

[33] Immunity and Safety of Covid-19 Synthetic Minigene Vaccine

https://clinicaltrials.gov/ct2/show/NCT04276896

[34] Safety and Immunity of Covid-19 aAPC Vaccine

https://clinicaltrials.gov/ct2/show/NCT04299724