COVID: presistence of virus in stool/sputum; and FDA authorizes chloroquine use

A recent study from China raised the potential continued infectivity of SARS-CoV-2 from stool and sputum up to 39 days after pharyngeal samples were negative (see covid pos sputum feces longterm AIM2020 in dropbox, or doi:10.7326/M20-0991)

Details:

-- 133 patients who were admitted to the hospital with documented Covid-19 infection, over a 5 week period

-- 22 of these patients had an initial or follow-up positive sputum or fecal sample for SARS-CoV-2 while having negative follow-up pharyngeal samples, per protocol below

    -- 545 specimens were collected from these 22 patients: 209 pharyngeal swabs, 262 sputum samples, and 74 feces samples

    -- 18 of these patients were 15-65 years old, 14 male, 11 had a history of the travel or exposure to an individual from Hubei province in the past month.

    -- 17 had no coexisting condition (of the other 5, 4 had hypertension, 2 diabetes, 1 COPD: ie, none had signficant immunocompromise)

    -- Fever was the most common presenting symptom. Covid-19 was diagnosed from 1 to 15 days after symptom onset 

-- hospital discharge was 15 to 60 days after symptom onset (average about 35 days)

-- 17 had mild pneumonia, 3 had uncomplicated illness, and 2 had severe/critical illness

-- these 22 patients were discharged from the hospital after meeting the following 4 criteria: afebrile for more than 3 days, resolution of respiratory symptoms, substantial improvement of chest CT, and 2 consecutive negative PCR tests for SARS-CoV-2 in respiratory samples obtained at least 24 hours apart

Results:

-- after the pharyngeal samples were negative:

    -- sputum samples remained positive for SARS-CoV-2 by PCR for up to 39 days

    -- feces samples remained positive by PCR for up to 13 days

Commentary:

-- the criteria for withdrawing isolation at this time from the CDC include 2 negative pharyngeal samples collected at least 24 hours apart, after symptoms of Covid-19 have subsided (eg, see http://gmodestmedblogs.blogspot.com/2020/03/guidelines-for-stopping-home-isolation.html )

-- though PCR can be positive after the organisms are no longer viable, these are remarkably extended times of PCR positivity, raising the question of viable transmissible organisms remaining in the sputum and feces for a long time after apparent clinical resolution and negative PCRs from the pharynx

-- in order for us to be sure that these patients had communicable virus, we should show that the virus seems to be viable (bearing in mind that our in vitro positive cultures do not necessarily track with infectious or transmissible viruses in humans); and that there are indeed actual cases of viral transmission through feces or sputum from patients who meet the definition for withdrawing isolation per the CDC (not easy to do: did the contact get the virus from being around the feces of the previous case, or perhaps other undiagnosed people or surfaces or air they came in contact with?? the virus does mutate quickly, so genetic tracking might be useful)

    -- however, a rather disturbing research letter in JAMA (see Lan L. JAMA. 2020. doi:10.1001/jama.2020.2783) from a hospital in Wuhan examined 4 healthcare workers who developed mild or moderate disease with Covid-19, and were discharged according to the same criteria as above, with suggested home-quarantine for 5 additional days. These healthcare workers had subsequent pharyngeal PCR tests 5 to 13 days later, and they were all positive. All patients had 3 repeat PCR tests performed over the next 4 to 5 days and all continued to be positive. These were repeated from a PCR test kit from a different manufacturer and were positive. None of their family members were infected and none reported any contact with persons with respiratory infections; and, particularly as health care workers, they took special care during their home quarantine

And, as a related issue, it seems that some patients have ocular symptoms with COVID-19 (conjunctival hyperemia, chemosis, epiphora, or increased secretions) and conjunctival samples (as well as nasopharyngeal samples) can be PCR-positive: see https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2764083 .  so, another possible source of viral communicability....

So, how do we interpret these data, understanding that we do not have cases of dccumented transmission in the setting of patients fulfilling the criteria for discharge above?

--is it that the PCR test itself is not so reliable?

-- Is it that the PCR test from nasopharyngeal tests are just not so reliable? (other studies have found that sputum is more reliably positive than pharyngeal samples)

-- Is it that patients harbor the virus in their sputum, which then re-colonizes the pharynx?

And, should this change our management?

-- Perhaps we should advise people to be extra careful not to contaminate their surroundings with fecal matter?

-- perhaps people should wear a mask for several weeks after recovery? And if so, for how long?

-- perhaps we should routinely recheck the PCR 5 or so days later and not consider the person as a potential viral vector unless this is positive? or maybe 10 days later as well?

It does seem that it would be useful to have cultures done to see if the virus were culturable/viable in vitro. If not, there would be less of an imperative to suggest these protective strategies

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also, the FDA just authorized the emergency use of chloroquine phosphate and hydroxychloroquine sulfate for treatment of COVID-19 in the absence of clinical trials, or participation is not feasible, noting that (quoted from https://www.fda.gov/media/136534/download ):

1. The SARS-CoV-2 can cause a serious or life-threatening disease or condition, including severe respiratory illness, to humans infected by this virus; 

2. Based on the totality of scientific evidence available to FDA, it is reasonable to believe that chloroquine phosphate and hydroxychloroquine sulfate may be effective in treating COVID-19, and that, when used under the conditions described in this authorization, the known and potential benefits of chloroquine phosphate and hydroxychloroquine sulfate when used to treat COVID-19 outweigh the known and potential risks of such products; and 

3. There is no adequate, approved, and available alternative to the emergency use of chloroquine phosphate and hydroxychloroquine sulfate for the treatment of COVID19.

geoff​

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