April 4th Covid-19 Literature Review

Steven Kornweiss, MD covid-19 Leave a Comment

Hydroxychloroquine (HCQ)

This paper seems to shed doubt on the safety and efficacy of this drug that we’re all hoping will work. The study was prospective and observational. Eleven patients were treated with the drug. Within 5 days of initiation, 1 patient died, 2 were transferred to the ICU, and another had treatment (HCQ) and Azithromycin were discontinued due to Qtc prolongation which puts the patient at risk for deadly arrhythmia.

Vaccine Development

This review paper discusses the various vaccine developments that are underway. I cannot glean a timeline from this review, but it does answer some questions as to who is doing what on this front. There is at last one trial in the US which will be enrolling adult volunteers within the next week (Moderna, Inc mentioned below).

  1. Recombinant Subunit Vaccine

    "Clover Biopharmaceuticals is pre-clinical testing a recombinant subunit vaccine based on the trimeric S protein (S-Trimer) of the SARS-CoV-2 [72]"

    "The University of Queensland is developing subunit vaccines using the "molecular clamp," a transformative technology [74]"

  2. DNA Vaccine

    "Inovio Pharmaceuticals, in collaboration with Beijing Advaccine Biotechnology, has started pre-clinical trials for DNA vaccine (INO-4800) against COVID-19 [78]"

  3. mRNA Vaccine

    "Moderna, Inc. has started phase I clinical trials for mRNA-1273, an mRNA vaccine, encoding viral spike (S) protein of SARS-CoV-2"

  4. Other

    "Genexine Inc. is developing a COVID-19 vaccine using Hyleukin-7 platform technology [84]"

Asymptomatic Transmission

This Paper published in the "International Journal of Antimicrobial Agents" puts forth an assertion that I’ve seen many times in the past few weeks…

"Besides, it has been reported that asymptomatic COVID-19 patients during their incubation periods can effectively transmit SARS-CoV2 [51, 52]"

This is now the view currently held by politicians, public health experts, physicians, and nurses and it is the basis for much of our behavior and protective gear policies within our hospitals. I think this is probably true, but it is far from being proven and it is likely true to various degrees depending on the context. Based on my current literature review, the evidence for asymptomatic/pre-symptomatic spread is limited to this study (and possibly a few other similar reports) which traced a German businessman who likely transmitted the virus to his contacts during his pre-symptomatic period.

Besides these reports, the other evidence is from stories such as this, in which members of a church choir were supposedly infected by an asymptomatic or presymptomatic member.

Airborne Transmission

Airborne transmission (persistence of infectious respiratory droplets which hang in the air for longer than seconds or minutes and can travel greater than 6 feet) is still debated as a cause of Covid-19 transmission.

From the available evidence, it seems that there is likely some limited amount of "airborne" transmission. This paper discusses one such scenario with air conditioning in a restaurant in China.

"Virus transmission in this outbreak cannot be explained by droplet transmission alone. Larger respiratory droplets (>5 μm) remain in the air for only a short time and travel only short distances, generally <1 m (2,3). The distances between patient A1 and persons at other tables, especially those at table C, were all >1 m. However, strong airflow from the air conditioner could have propagated droplets from table C to table A, then to table B, and then back to table C (Figure). Virus-laden small (<5 μm) aerosolized droplets can remain in the air and travel long distances, >1 m (4). Potential aerosol transmission of severe acute respiratory syndrome and Middle East respiratory syndrome viruses has been reported (5,6). However, none of the staff or other diners in restaurant X were infected. Moreover, the smear samples from the air conditioner were all nucleotide negative. This finding is less consistent with aerosol transmission. However, aerosols would tend to follow the airflow, and the lower concentrations of aerosols at greater distances might have been insufficient to cause infection in other parts of the restaurant."

Overall, in every-day conditions, it seems that the two major transmission mechanisms are respiratory droplets – relatively large droplets containing viral particles which travel 1-2 meters and then fall to the ground. There are scenarios in which smaller droplets might travel farther or be suspended in the air longer (see this NEJM article on aerosols, and this JAMA article on sneezes.

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