CLINICAL AND MICROBIOLOGICAL PROFILE OF

SARS CoV-2 INFECTION IN HARYANA

Abstract
In the beginning of December 2019 a series of pneumonia cases of unknown origin were identified
in Wuhan, the capital city of Hubei province. On further workup and investigation etiological agent
came out to be enveloped RNA beta corona virus labeled as novel corona which later on named as
severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). This agent affect nearly 210
countries in world.
 INTRODUCTION & REVIEW OF LITERATURE

In the beginning of December 2019 pneumonia case of unknown origin were identified in Wuhan,
the capital city of Hubei province. However on Dec 31 China reports a cluster of cases of
pneumonia with unknown etiology in Wuhan to WHO. On 7th January 2020 pathogen identified
as a novel enveloped RNA beta corona virus also named as severe acute respiratory syndrome
corona virus 2 (SARS-CoV2). On Jan 30th WHO declared it as a “public health emergency of
international concern” and on March 11 WHO declared it as Pandemic.[1] On 30th Jan 2020 first
case of SARS CoV2 was identified in Kerala in INDIA. In India till now there is 8988 active cases,
1035 cases has been discharged/ cure, 339 death has been occur till now. In Haryana till now there
is 185 total confirmed cases in which 29 cases has been cured/discharged/migrated with 3 death.[2]
Corona viruses are large family of viruses having family Coronaviridae which includes two
subfamilies Coronavirinae and Torovirinae. Species from Coronavirinae affects human causing
wide spectrum of illnesses ranging from mild common cold to more severe pandemic respiratory
disease like SARS and MERS. Species from Torovirinae usually affect terrestrial and aquatic
animals.[3] Corona viruses are enveloped non segmented positive sense RNA virus. Corona virus
virions are usually spherical in shape with club shaped spike projections from their surface which
gives them solar corona like appearance. Corona virus particle consists of mainly four structural
proteins which are spike (S) protein, membrane (M) protein, envelope (E) protein, and
nucleocapside (N) protein.
In most of Corona virus species, S protein breaks into S1 polypeptide domain, which
makes the large receptor binding domain of the S protein and S2 polypeptide domain, which
forms the stalk of the spike molecule. M protein is most abundant and provide shape to virion. E
protein is very divergent in nature, responsible for assemble and release of virus and thus role in
pathogenesis. N protein is responsible for binding of RNA in vitro. A subset of β-corona viruses
contain additional protein hem-agglutinin esterase (HE) thought to enhance S protein mediated
cell entry.[4] Recent studies suggest that Novel corona virus 2019 is a new human-infecting β
Coronavirus different from SARS CoV. Phylogenetic studies showed Covid 19 belongs to
subgenus Sarbecovirus, most closely related to bat-SL-CoVZC45 and bat-SL-CoVZXC21. Also
outbreak in Wuhan might be initially hosted by bats, and might have been transmitted to humans
via currently unknown wild animals sold at the Huanan seafood market. Molecular modeling study
showed structural similarity between the receptor-binding domains of Covid 19 and SARS CoV.
Covid 19 might use ACE2 as the receptor, despite the presence of amino acid mutations in the
2019-nCoV receptor-binding domain.[5]
Covid 19 is likely to be a zoonotic. However study is going on to find out the reservoir host and
intermediate carrier which spread infection to human. Initially bat was thought to be reservoir.
Also human to human transmission is well established through close contact or via droplet
infection of infected person.[6]
In host cell S protein binds to ACE2 receptor. then there is conformation change in the S protein
that enhance fusion of viral envelope with the cell membrane. Then Virus releases its RNA into
the host cell. later on Genome RNA is translated into viral replicase polyproteins pp 1a and pp
1ab, which are then cleaved into small products by viral proteinases. The polymerase produces a
series of sub genomic mRNAs by discontinuous transcription and finally translated into relevant
viral proteins. Viral proteins and genome RNA are subsequently assembled into virions in the ER
and Golgi and then transported via vesicles and released out of the cell.[7]
Clinical manifestation may be range from asymptomatic to severe ARDS. Clinical presentations
includes fever, dry cough, sore throat, shortness of breath, chest tightness, malaise, headache,
diarrhoea, nausea vomiting . Sometime patient may present with serious clinical spectrum like
ARDS multi organ failure manifestations like sepsis, septic shock or MODS. [8][9] Study conducted
by Huang et al, conducted in 41 patient show fever on 98%/, cough in 76%, myalgia and fatigue
in 44%, headache in 8%, Hemoptysis in 5%, dyspnoea in 55% , ARDS in 29% and acute cardiac
injury in 12% later on.[8]
A study by Guan W in 1099 subject shows the most common symptoms were fever in 43.8% on
admission and 88.7% during hospitalization and second most common symptom was cough in
67.8%, fatigue in 38.1%, shortness of breath in 18.7% sore throat in 13.9%, Diarrhea was less
common in 3.8%.[9]
Another study by Wu Z et al in 72314 cases, classified illness into
• Mild disease: non-pneumonia and mild pneumonia; seen in 81% of cases.
• Severe disease : dyspnea, respiratory frequency ≥ 30/min, blood oxygen saturation (SpO2)
≤ 93%, PaO2/FiO2 ratio or P/F [the ratio between the blood pressure of the oxygen (partial
pressure of oxygen, PaO2) and the percentage of oxygen supplied (fraction of inspired
 oxygen, FiO2)] < 300, and/or lung infiltrates > 50% within 24 to 48 hours; this seen in 14%
of cases.
• Critical disease: respiratory failure, septic shock, and/or multiple organ dysfunction
(MOD) or failure (MOF); seen in 5% of cases.[1]
As per Government of India Ministry of Health & Family Welfare Directorate General of Health
Services Guidelines on Clinical Management of COVID – 19
Clinical syndromes associated with COVID - 19 infection
Uncomplicated illness : Patients with uncomplicated upper respiratory tract viral infection, may
have non-specific symptoms such as fever, cough, sore throat, nasal congestion, malaise,
headache. The elderly and immuno-suppressed may present with atypical symptoms. These
patients do not have any signs of dehydration, sepsis or shortness of breath.
Mild pneumonia : Patient with pneumonia and no signs of severe pneumonia. Child with non-
severe pneumonia has cough or difficulty in breathing/ fast breathing: (fast breathing - in
breaths/min):
<2 months, ≥60;
2–11 months, ≥50;
1–5 years, ≥40 and no signs of severe pneumonia
Severe pneumonia
• Adolescent or adult : fever or suspected respiratory infection, plus one of the following;
respiratory rate >30 breaths/min, severe respiratory distress, SpO2 <90% on room air
• Child : cough or difficulty in breathing, plus at least one of the following: central cyanosis
or SpO2 <90%; severe respiratory distress (e.g. grunting, chest in-drawing); signs of
pneumonia with any of the following danger signs: inability to breastfeed or drink, lethargy
or unconsciousness, or convulsions. Other signs of pneumonia may be present: chest
indrawing, fast breathing (in breaths/min): <2 months ≥60; 2–11 months ≥50; 1–5 years
≥40. The diagnosis is clinical; chest imaging can exclude complications
Acute Respiratory Distress Syndrome
• Onset: new or worsening respiratory symptoms within one week of known clinical insult.
• Chest imaging (radiograph, CT scan, or lung ultrasound): bilateral opacities, not fully
explained by effusions, lobar or lung collapse, or nodules.
 • Origin of edema: respiratory failure not fully explained by cardiac failure or fluid overload.
Need objective assessment (e.g. echocardiography) to exclude hydrostatic cause of edema
if no risk factor present.
• Oxygenation (adults):
▪ Mild ARDS: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg (with PEEP or CPAP
≥5 cm H2O, or non-ventilated)
▪ Moderate ARDS: 100 mmHg < PaO2/FiO2 ≤200 mmHg with PEEP ≥5 cm
H2O, or non-ventilated)
▪ Severe ARDS: PaO2/FiO2 ≤ 100 mmHg with PEEP ≥5 cm H2O, or non-
ventilated)
▪ When PaO2 is not available, SpO2/FiO2 ≤315 suggests ARDS (including
in non-ventilated patients)
• Oxygenation : (children)
(note OI = Oxygenation Index and OSI = Oxygenation Index using SpO2)
▪ Bilevel NIV or CPAP ≥5 cm H2O via full face mask: PaO2/FiO2 ≤ 300 mmHg or
SpO2/FiO2 ≤264
▪ Mild ARDS (invasively ventilated): 4 ≤ OI < 8 or 5 ≤ OSI < 7.5
▪ Moderate ARDS (invasively ventilated): 8 ≤ OI < 16 or 7.5 ≤ OSI < 12.3
▪ Severe ARDS (invasively ventilated): OI ≥ 16 or OSI ≥ 12.3
Sepsis
▪ Adults: life-threatening organ dysfunction caused by a dysregulated host response to
suspected or proven infection, with organ dysfunction. Signs of organ dysfunction include:
altered mental status, difficult or fast breathing, low oxygen saturation, reduced urine
output, fast heart rate, weak pulse, cold extremities or low blood pressure, skin mottling,
or laboratory evidence of coagulopathy, thrombocytopenia, acidosis, high lactate or
hyperbilirubinemia.
▪ Children: suspected or proven infection and ≥2 SIRS criteria, of which one must be
abnormal temperature or white blood cell count

Septic shock
 ▪ Adults: persisting hypotension despite volume resuscitation, requiring vasopressors to
maintain MAP ≥65 mmHg and serum lactate level < 2 mmol/L
▪ Children: any hypotension (SBP <5th centile or >2 SD below normal for age) or 2-3 of
the following: altered mental state; bradycardia or tachycardia (HR <90 bpm or >160 bpm
in infants and HR <70 bpm or >150 bpm in children); prolonged capillary refill (>2 sec) or
warm vasodilation with bounding pulses; tachypnea; mottled skin or petechial or purpuric
rash; increased lactate; oliguria; hyperthermia or hypothermia[10]
On the basis of sign and symptom patient undergo a series of testing. At time of presentation
complete Hemogram which show lymphocytopenia, thrombocytopenia, leukopenia. There is also
elevation of C reactive protein, AST, ALT, derange renal function, raised D dimer, serum ferritin
level. Radiological investigation suggest ground-glass opacity ,bilateral patchy shadowing, local
patchy shadow more in CT chest than on chest x-ray, however they may be normal in some
patient.[9]
Quantitative real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay has been
widely used for the detection from respiratory secretions and final pathogenic diagnostics of
COVID‐19.[11]
In India as per ICMR Strategy for COVID19 testing in India, Version 4, released on 09/04/2020
1. All symptomatic individuals who have undertaken international travel in the last 14 days
2. All symptomatic contacts of laboratory confirmed cases
3. All symptomatic health care workers
4. All patients with Severe Acute Respiratory Illness (fever AND cough and/or shortness of breath)
5. Asymptomatic direct and high-risk contacts of a confirmed case should be tested once between
day 5 and day 14 of coming in his/her contact
In hotspots/cluster and in large migration gatherings/ evacuees centers
6. All symptomatic ILI (fever, cough, sore throat, runny nose)
a. Within 7 days of illness – rRT-PCR
b. After 7 days of illness – Antibody test (If negative, confirmed by rRT-PCR)[12]

Regarding treatment of Covid 19 as such there is no specific treatment for it.

A recent open-label nonrandomized study done in France on 36 patients (20 in the
hydroxychloroquine group and 16 in the control group) reported significant fall in viral load with
hydroxychloroquine, 200 mg compared with control patients receiving standard supportive care.
Also addition of azithromycin to hydroxychloroquine in 6 patients resulted in significant viral
clearance (6/6, 100%) compared with hydroxychloroquine monotherapy (8/14, 57%).[13]
A study by Cao and colleagues in 199 COVID-19 patient reported the results of an open-
label RCT comparing the efficacy of lopinavir / ritonavir vs standard care show the primary
outcome of time to clinical improvement defined by a 2-point improvement on a 7-category ordinal
scale or hospital discharge was similar in both group with hazard ratio [HR], 1.31 [95% CI, 0.95-
1.85]; P = .09). Also there is no significant differences in viral clearance or 28-day mortality rate
were observed. however RCTs of lopinavir/ritonavir are ongoing, the current data suggest a limited
role for lopinavir/ritonavir in COVID-19[14]
Remdesivir is aminophosphate prodrug showing potential therapy for COVID-19 due to
its broad-spectrum. positive result of remdesivir for COVID-19 has been reported in case
reports.[15][16]
However there are various of RCT has been done but none of them is FDA approved for treatment
of COVID-19.

MATERIAL AND METHODS

This will be a cross sectional study carried out at Department of Medicine, PGIMS, Rohtak , India.
Patients admitted in isolation ward of PGIMS, Rohtak will be enrolled in this study, after taking
written informed consent. Patient presented with Severe Acute Respiratory Illness (SARI) with
history of any of following in last 14 days
1. History of fever > 380 C
2. Cough/sore throat
3. Hypoxia (saturation <94%)
4. Systolic BP <90mmHg or diastolic BP <60 mmHg
5. GCS <15
will be screened at flu clinic. Those who are tested positive by RT PCR method will be admitted
in isolation ward. Patient will be categorized into 3 category as per ICMR.
Category A - Mild symptoms and none of following
1. Hypoxia ( saturation <94% on room air)
2. Respiratory rate >22/minute
3. Systolic BP <90mmHg or diastolic BP <60 mmHg
4. Heart rate > 110/minute
5. Fever >1010F
6. GCS <15
Category B - Moderate symptoms : Fever >1010F or Heart rate > 110/minute and none of following
1. Hypoxia ( saturation <94% on room air)
2. Respiratory rate >22/minute
3. Systolic BP <90mmHg or diastolic BP <60 mmHg
4. GCS <15
Category C - Severe disease : Any two of following
1. Hypoxia ( saturation <94% on room air)
2. Respiratory rate >22/minute
3. Systolic BP <90mmHg or diastolic BP <60 mmHg
4. GCS <15
5. Worsening co-morbid conditions requiring emergency care
6. Pregnancy related issues.
7. Surgical Problems.
 Category A and B will be treated in Isolation ward / HDU on O 2 and Category C patient
will be treated in ICU setting. All patients will be given treatment as per ICMR protocol. Baseline
ECG will be done to document QTc and its further management
1. Category A - Only symptomatic treatment
2. Category B - Chloroquine / HCQ : Dose of chloroquine 500 mg twice daily for 10 days Or
Lopinavir/ Ritonavir : Lopinavir/ Ritonavir (400 mg/100 mg) given orally , twice
daily for 14 days ( After approval from HOD medicine and HOD PCCM)
3. Category C : To be managed in ICU.
All patient will be monitored for complication including ARDS, Pulmonary thromboembolism,
DVT, Renal failure. On developing any complication standard protocol will be used for treatment.
Patient will be look for primary outcome which are cure and death. Secondary outcome includes
complication like ARDS, myocarditis renal failure, ICU requirement, dialysis required, hospital
stay days, incubation - death (days), incubation - death (days).

Statistical Analysis:
 Data will be recorded carefully and will be entered in a master chart prepared using
Microsoft Excel 2016. For all descriptive and statistical analysis, Statistical Package for Social
Sciences (SPSS) Version 23 will be used. An SPSS syntax file that automatically checks, recodes
data and computes domain scores is used. The distribution of data will be analyzed to assess for
parametric versus non-parametric analysis. The values of all domains will be expressed in mean
and standard deviation, for each group separately. All categorical variables will be expressed in
number out of total and their respective percentages. For all tests, p value of less than 0.05 will be
considered as significant and confidence level would be kept at 95percent.

PATIENT CONSENT FOR INCLUSION TO STUDY

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Patients have right not to sign this consent form : refusal to sign the form will not affect their
care in any way
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I________________________________________________ hereby give my consent for
inclusion for study entitled “CLINICAL AND MICROBIOLOGICAL PROFILE OF SARS CoV-2
INFECTION IN HARYANA .”

I have been told the details of study plan and I understand the methodology. I hereby given
my consent for clinical information and other details/investigation of my case may be published
in any medical journal/medical books or online medical website by the convener of this study. As
a result I understand that material may be seen by general population. I understand that my name,
initials and address will not be published but that anonymity cannot be guaranteed. I am willing to
participate in this study and available for follow up as needed. I can withdraw from this study at
any time at my willingness.

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gwaa fd eq>s 'kks/k dk;Z “SARS COV-2 के नैदाननक और सूक्ष्म जीव ववज्ञान जानकारी की हररयाणा में ”
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nsrk@nsrh gWwa fd esjs ls lEcfU/kr dksbZ Hkh lwpuk fdlh Hkh fpfdRlh; tuZy vFkok fdrkc esa Nkih
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Name of Patient Name of Witness

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Signature Signature
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PATIENT PROFORMA
S. No: -_________ Date of Admission : -______________

Date of discharge: -____________

Name and Address : -

Age : - Sex : -

Mobile no : - Occupation : -

Socio-economic status (Modified Kuppuswami Scale): - 1. Upper 2. Upper Middle

3. Lower Middle 4. Upper Lower
5. Lower

Income per month :- - 1. <2,000 2. 2,000-6,000

3. 6,000-15,000 4. 15,000-30000
5. 30000-50000 6. > 50000

Marital status: - 1. Married 2. Unmarried

3. Divorced 4. Widowed

Travel History : 1. International

2. National

History of Contact of infected Covid 19 :

Suspected Source : 1. International Travel

2. Contact with symptomatic Covid
3. Symptomatic Health Care
4. Contact with Large social or religious gathering
5. Admit with SARI
6. Not known

CLINICAL HISTORY
Presenting complaints: -

 Fever
 cough
 Shortness of breath
 Chest Pain
 Sore throat
 Myalgia
 Fatigue
 Hemoptysis
 Headache
 If any others ( Specify)

Co morbidities: -
 Hypertension
 DM
 IHD
 COPD/ Asthma
 CKD
 If any others (Specify) :

EXAMINATION
GENERAL PHYSICAL EXAMINATION : - 1. Height 2. Weight
3. BMI

VITALS : - Blood pressure__________ Pulse rate_________ Respiratory rate_______

Pallor : Icterus: Cyanosis: Clubbing:

JVP: Pedal edema : Lymphadenopathy:
O2 Saturation : Temperature :

SYSTEMIC EXAMINATION
• Cardiovascular System Examination

 Heart Sound
 Murmur
 Pericardial rub
• Respiratory System Examination
 Normal Breathing
 Associated Sounds : Rhonchi / Crepts /Bronchial Sound/

Pleural Rub

• Abdominal Examination

 Collaterals
 Organomegaly
 Fluid

• Central Nervous System Examination

 GCS -

• Others
INVESTIGATIONS
PARAMETER ON DAY 1 DAY 3 DAY 7 DAY 14 ON
ADM. DIS.
Hemoglobin

TLC

DLC

N/L RATIO

PLT

PBF
TYPE
MALARIA
B. UREA

B.SUGAR

S.CREATININE

S.SODIUM

S.POTASSIUM

SGOT

SGPT

ALP

S.BILIRUBIN
T/D/I
S.PROTEIN

S.ALBUMIN

A:G

ICU PARAMETERS
 • BLOOD GAS ANALYSIS :
PARAMETER
PH
PAO2
PCO2
HCO3-

PAO2/FIO2
O2
SATURATION

• HIV
• ANTI-HCV
• HBsAg

SPECIAL INVESTIGATION AT TIME OF ADMISSION AND DISCHARGE

• CRP :-
• S .PROCALCITONIN (OPTIONAL) :-
• D-DIMER :-
• TROP I :-
• LDH :-
• RT PCR :-
➢ ON DAY OF ADMISSION :-
➢ 2ND DAY (IF REQUIRED) :-
➢ 3RD DAY (IF REQUIRED) :-
➢ BETWEEN 5-14 DAY :-

• ECG:

• CHEST X-RAY :
• CT CHEST (OPTIONAL)
• CATEGORY (A/B/C)
• TREATMENT GIVEN
➢ DRUG
 HCQ
 AZITHROMYCIN
 OTHERS
➢ OXYGEN SUPPLY MODE
 NASAL PRONGS
 VENTURIMASK
 HIGH FLOW OXYGEN CHAMBER
 NIV
 INVASIVE VENTILATOR
• OUTCOME
➢ PRIMARY
 CURE
 DEATH
➢ SECONADARY
 COMPLICATION
 ICU REQUIREMENT
 DIALYSIS REQUIRED
 HOSPITAL STAY DAYS
 INCUBATION - DEATH (DAYS)
 INCUBATION - DEATH (DAYS)

FINAL IMPRESSION :

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