Quantitative and Prognostic Aspects of COVID19:

Quantitative aspects of SARS-CoV-2 causing COVID19. They have been collected by a detailed review of different review articles on this topic from Italy, China and Korea.

Origin:
Presumed to originate from Bats via the unknown intermediate host. The genetic sequence of the COVID-19 showed more than 80% identity to SARS-CoV and 50% to the MERS-CoV. 

Mode of Transmission:
Droplets, which do not travel more than six feet. Not airborne but in one letter to the editor, SARS-CoV-2 remained viable in aerosols under experimental conditions for at least three hours.

Entry into the Host:
Enters the host cell via ACE-2 (angiotensin-converting enzyme mostly expressed in the lungs) by forming the ACE-gene receptor complex.

Pathogenesis:
Inflammatory mediators including Cytokine and chemokines are the basis of the pathogenesis of COVID19 related complications. They include IL2, IL6, IL7, IL10, GCSF and TNFα and many more. ( cytokine storm leading to ARDS, septic shock and multiorgan failure. One of the bases of Tocilizumab; an IL 6 inhibitor being investigated).

Clinical Spectrum:

a. Mild disease 80 %: Low grade or subclinical fever with a dry cough, flu-like symptoms. Please note that the definition of subclinical fever is 99.5 F in all WHO and ASGE warning and screening guidelines to the GI staff not 100.4F)

b. Moderate Disease: 15 %: Shortness of breath, hypoxia needing hospitalization and O2.

c. Severe disease: 5 %: ARDS, pneumonia, septic shock, multiorgan failure requiring ICU.

The Onset of Symptoms:
2.5 % develop symptoms in 2.2 days after exposure. 97.5 % patients develop in 11.5 days. The median incubation period is 5.2 days. Symptoms correlate with the viral shedding.

Viral Shedding:
The median duration of viral RNA shedding from oropharyngeal specimens was 20 days (range of 8 to 37 days). It depends on the severity of the disease. In mild disease, 90 % had negative repeat PCR from nasopharyngeal swabs by 10 days after the symptom onset. The tests were positive for a longer period in patients with more severe illness.

Infectivity:
R- naught (reproduction unit) is 2.2 (Spanish flu 1.8, Ebola 1.5-2.5, influenza 2-3). According to a joint WHO-China report, the rate of secondary COVID-19 ranged from 1 to 5 percent among tens of thousands of close contacts of confirmed patients in China.

Hospitalization: 
The rate of hospitalization is 20 %. (as 80 % are mild, and do not need hospitals rather need home isolation).

Pneumonia:
45 % of patients who are hospitalized had pneumonia > 50 percent lung involvement on imaging.

ICU Admission:
12 percent of all the detected COVID-19 cases and 16 percent of all the hospitalized patients were admitted to the intensive care unit.

ARDS:
20-41% of the patients who are hospitalized develop ARDS on a median day 8 requiring mechanical ventilation. ARDS developed in 61 % of the COVOD19 patients admitted to ICU. Diabetes mellitus and hypertension were each associated with the ARDS in all the studies.

SeverityPredictor:
Very interestingly, detection of the virus in the blood (serum PCR positive) in the mild disease was found to be a predictor of upcoming severe disease in one case series (8 out of 8 patients).

Extubation:
50 % of the CoVID19 related ARDS got extubated. 50 % died in Italian and Chinese reports.

Mortality:
The overall case-fatality rate was 2.3 percent. However, the rate ranged from 5.8 percent in Wuhan to 0.7 percent in the rest of China.

Age:
Of 44,500 confirmed infections in China, 87 percent of patients were between 30 and 79 years old. The median age in Italy was 65 and South Korea was 40. Old age was an independent predictor of mortality with case fatality rates of 8 % and 15 % among those aged 70 to 79 years and 80 years or older, respectively.

Comorbidities:
In a subset of 355 patients who died with COVID-19 in Italy, the mean number of pre-existing comorbidities was 2.7, and only 3 patients had no underlying condition.

Recovery:
According to the WHO, recovery time appears to be around two weeks for mild infections and three to six weeks for severe disease.

Reinfection:
Four such cases were identified who clinically improved and were tested negative as a test of cure, but were found to be positive again later when tested upon developing the symptoms again. This points to the re-infection with different serotypes.

Serotypes:
Two different serotypes were identified in Wuhan. L-type that is more common 70 %, S-type that infects in 30 % of cases. Their clinical significance is not known, except for the hypothesis of reinfection.

False Negative Results:
NAAT using the R-PCR technique is used for diagnosis. It depends on the source of the sample. BAL has the highest sensitivity of 95 %, then tracheal aspirate, then sputum and then nasopharyngeal swab which is 71 %.  The oropharyngeal swabs have the lowest sensitivity of 32 % in one study. In one study when PCR was negative times two, but the clinical suspicion was high, another modality IgM antibody using ELISA was used.  The ELISA-IgM test was positive in 90 % of such cases. Possible causes of false-negative results are the inability of PCR to target at least two gene targets out of known 4, poor handling of the sample, more proximal sample location in the respiratory tract and virus mutation causing reverse transcriptase PCR enzyme inhibition.

Treatment:

Mild disease: home quarantine. Prevent the spread.

Moderate to Severe disease: Supportive therapy in hospitals and ICU.

Antimicrobials Anti-inflammatory Options:
A big trial named SOLIDARITY trial is going on investigating and comparing Remdesivir, HCQ, chloroquine, Kaletra with INF-Beta. So far this much is known in order of the efficacy:

 a. Remdesivir has shown maximum in vitro activity, so far, against COVID19 by inhibiting RNA- dependent RNA polymerase. The first COVID19 case of UA was given Remdesivir on day 7 due to his moderate disease, and he remarkably improved on day 8 and viral loads remarkably decreased in the next 5 days

b. HCQ (400 mg daily) was compared with no treatment in 138 patients: 72 % of those who were treated had virus-negative on day 6 vs 12.5 % of supportive care.

c. This efficacy of HCQ is increased when used with Azithromycin. But both these drugs increase QTc interval. Since 29 % of the severe COVID19 patients may have a myocardial injury, these drugs may have worse outcomes in severe disease.

d. Chloroquine is relatively less effective than HCQ in vitro. 

e. Tocilizumab being studied in cytokine storm and ARDS due to its IL-6 inhibitor features.

f. Convalescent Plasma: Used previously for SARS-CoV-1, Middle East respiratory syndrome, Ebola, and H1N1 influenza with reported success. The safety and efficacy of convalescent plasma transfusion in COVID19 are still under study.

g. Kaletra alone has proven no more effective than a placebo. It is being tested combined with INF-beta in the SOLIDARITY trial

Chemoprevention:
No pre or post-exposure chemoprophylaxis is yet approved.

NSAIDs and ACE inhibitors and Mortality: Anecdotal experiences of high mortality while using NSAIDs and ACE/ARB inhibitors have been reported. However, there is no evidence so far to recommend discontinuing ACE/ARBs rather there is a concern if we discontinue them, the diabetic nephropathy, CHF and HTN may go uncontrolled which are known risk factors for COVID19 mortality.

WhentoDiscontinueQuarantine:
Symptomatic patients can discontinue quarantine:

a. after 3 days after the complete resolution of symptoms (fever, cough) and

b. after 7 days after the onset of the symptoms (Remember: both conditions should be met. That means minimum Quarantine is >7 days.)

If repeat testing is done to document the clearance, the patient can be relieved from the quarantine if:

a. symptoms resolve and

b. the two nasopharyngeal PCR tests were done 24 hrs apart are negative. Again both conditions should be met.

Asymptomatic Carrier:
No study knows the percentage of this category. They are exposed but do not develop symptoms and clear the virus without being symptomatic. If the patient is asymptomatic but tested positive for COVOD19 due to high-risk area travel history, they can discontinue quarantine 7 days after the test date.

Objective Findings in Asymptomatic Patients:
Even patients with asymptomatic infection may have objective clinical abnormalities (50 percent had typical ground-glass opacities or patchy shadowing on CT chest in 700 of the lab-confirmed asymptomatic COVOD19 patients of Yokohama Cruise).

GI Involvement:
1-5 % of cases have GI symptoms, LFTs abnormality and stool were positive for COVID-19. The First COVID19 case of the USA in the state of WA had GI symptoms and stool positive for SAARS-Co2 PCR on day 6.

Pregnancy:
No real concerns have been noted in pregnant females and their fetuses except preterm delivery if the mother is severely sick.