Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States

Abstract

Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously^1-3. Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21-68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness.

Extended Data Fig. 1 |. Patient 6 laboratory and clinical values, symptoms, and SARS-CoV-2 rRT-PCR results during hospitalization.

Aminotransferase levels, maximum daily body temperature, minimum daily oxygen saturation, maximum daily oxygen requirement, symptoms, and rRT-PCR results are shown for hospitalization. Pink shading indicates remdesivir administration. Cycle threshold (Ct) values are shown for positive rRT-PCR tests. Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; SpO2, oxygen saturation; op, oropharyngeal; np, nasopharyngeal; neg, negative; inc, inconclusive.

Extended Data Fig. 2 |. Patient 7 laboratory and clinical values, symptoms, and SARS-CoV-2 rRT-PCR results during hospitalization.

Aminotransferase levels, maximum daily body temperature, minimum daily oxygen saturation, symptoms, and rRT-PCR results are shown for hospitalization. Cycle threshold (Ct) values are shown for positive rRT-PCR tests. Red text indicates decreasing Ct values. Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; SpO2, oxygen saturation; op, oropharyngeal; np, nasopharyngeal; neg, negative; inc, inconclusive.

Extended Data Fig. 3 |. Patient 8 laboratory and clinical values, symptoms, and SARS-CoV-2 rRT-PCR results during hospitalization.

Aminotransferase levels, maximum daily body temperature, minimum daily oxygen saturation, maximum daily oxygen requirement, symptoms, and rRT-PCR results are shown for hospitalization. Pink shading indicates remdesivir administration. Cycle threshold (Ct) values are shown for positive rRT-PCR tests. Red text indicates decreasing Ct values. Patient has a chronic cough that had returned to baseline starting day 11. Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; SpO2, oxygen saturation; op, oropharyngeal; np, nasopharyngeal; neg, negative; inc, inconclusive.

Extended Data Fig. 4 |. Patient 9 laboratory and clinical values, symptoms, and SARS-CoV-2 rRT-PCR results during hospitalization.

Aminotransferase levels, maximum daily body temperature, minimum daily oxygen saturation, maximum daily oxygen requirement, symptoms, and rRT-PCR results are shown for hospitalization. Pink shading indicates remdesivir administration. Cycle threshold (Ct) values are shown for positive rRT-PCR tests. Red text indicates decreasing Ct values. Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; SpO2, oxygen saturation; op, oropharyngeal; np, nasopharyngeal; neg, negative; inc, inconclusive.

Extended Data Fig. 5 |. Patient 10 laboratory and clinical values, symptoms, and SARS-CoV-2 rRT-PCR results during hospitalization.

Aminotransferase levels, maximum daily body temperature, minimum daily oxygen saturation, maximum daily oxygen requirement, symptoms, and rRT-PCR results are shown for hospitalization. Cycle threshold (Ct) values are shown for positive rRT-PCR tests. Red text indicates decreasing Ct values. Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; SpO2, oxygen saturation; op, oropharyngeal; np, nasopharyngeal; neg, negative; inc, inconclusive.

Extended Data Fig. 6 |. Patient 11 laboratory and clinical values, symptoms, and SARS-CoV-2 rRT-PCR results during hospitalization.

Aminotransferase levels, maximum daily body temperature, minimum daily oxygen saturation, maximum daily oxygen requirement, symptoms, and rRT-PCR results are shown for hospitalization. Cycle threshold (Ct) values are shown for positive rRT-PCR tests. Red text indicates decreasing Ct values. The patient had a positive nasopharyngeal swab on day 9 with Ct value of 35.1 (not shown). Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; SpO2, oxygen saturation; op, oropharyngeal; np, nasopharyngeal; neg, negative; inc, inconclusive.

Extended Data Fig. 7 |. Patient 12 laboratory and clinical values, symptoms, and SARS-CoV-2 rRT-PCR results during hospitalization.

Aminotransferase levels, maximum daily body temperature, minimum daily oxygen saturation, maximum daily oxygen requirement, symptoms, and rRT-PCR results are shown for hospitalization. Cycle threshold (Ct) values are shown for positive rRT-PCR tests. Red text indicates decreasing Ct values. Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; SpO2, oxygen saturation; op, oropharyngeal; np, nasopharyngeal; neg, negative; inc, inconclusive.

Extended Data Fig. 8 |. SARS-CoV-2 average Ct values for patients with COVID-19, by hospitalization status and specimen type.

For rRT-PCR-positive specimens, the average cycle threshold (Ct) value was calculated from the Ct values of three targets on the gene encoding the N protein. ‘Not detected’ indicated rRT-PCR-negative specimens. Inconclusive specimens were depicted as such; average Ct values were not calculated for these specimens. Categories for illness severity included a, not hospitalized, b, hospitalized with no supplemental oxygen, and c, hospitalized with supplemental oxygen. Specimen types depicted included nasopharyngeal (NP) swab, oropharyngeal (OP) swab, sputum, serum, and stool. Urine was not depicted because no specimens tested positive by rRT-PCR. Days are sequential from day of symptom onset (Day 1).

Extended Data Fig. 9 |. Phylogenetic tree.

A maximum-likelihood tree of SARS-CoV2 using selected full genome sequences from GISAID as of February 12, 2020. Strains are denoted by country (city for China when available), GISAID accession ID, date of collection and Patient ID in parentheses. Tips in red denote sequences from US cases. Bootstrap values of statistical support (50%) are shown as percentage equivalents.

Fig. 1 |. Timeline of illness onset, SARS-CoV-2 RNA detection, hospitalization, oxygen requirement and reported symptom resolution among the first 12 patients with COVID-19 in the United States, January to February 2020.

Patients 1–5 were not hospitalized and patients 6–12 were hospitalized. Days are sequential from day of symptom onset (day 1). Light blue bars indicate time patients were under home isolation. Yellow bars indicate duration of hospitalization. Dark blue bars indicate duration of supplemental oxygen administration in hospital. The orange dashed bar indicates duration of intensive care unit (ICU)-level monitoring for patient 9. The black ‘+’ indicates collection date of the earliest sample that tested positive for SARS-CoV-2 by rRT–PCR. The black asterisk indicates collection date of the latest sample tested by CDC with a positive result for SARS-CoV-2 by rRT–PCR. The orange diamond indicates date of last report of symptoms. The black square indicates the last day of isolation precautions. Patient 9 was isolated in a healthcare facility for the full time period; they were discharged from the first healthcare facility on day 27 and subsequently transferred to a second healthcare facility for public health purposes. Patient 1 reported a cough with initial onset in mid-December before the patient traveled to China. The patient reported no change in the cough from the initial onset until reported resolution on day 14. Because onset date was difficult to determine for this patient, we have used date of detection as day 1 to assess viral RNA detection.

Fig. 2 |. Clinical and laboratory values by illness day for the first seven patients hospitalized with COVID-19 in the United States, January to February 2020.

Clinical and laboratory values collected during hospitalization are shown for seven hospitalized patients by illness day. Values include oxygen saturation (SpO₂), supplemental oxygen requirement (O₂ req), maximum body temperature (T_max), AST, ALT and white blood cell (WBC) count. Pink shading indicates days of remdesivir administration for three patients. Dotted lines show fever threshold of 100.4 °F (T_max), 40 U l⁻¹ for AST and ALT, 4,000 cells per μl for WBC and 150 and 250 10³ mm⁻³ for platelets.

Fig. 3 |. SARS-CoV-2 rRT–PCR results by specimen type and day among the first 12 patients with COVID-19 in the United States, January to February 2020.

Specimen types tested include NP swab, OP swab, sputum, serum, stool and urine. Days are sequential from day of symptom onset (day 1). Viral culture was attempted on selected respiratory specimens collected early in the course of illness. rRT–PCR results were reported as positive (all three targets positive), negative (all three targets negative) or inconclusive (only one or two positive targets). Black-filled circles indicate rRT–PCR-positive specimens. Black-outlined circles indicate rRT–PCR-negative specimens. Gray-filled circles indicate specimens with inconclusive rRT–PCR results. Red squares surrounding black-filled circles indicate rRT–PCR-positive specimens from which viral culture was successful. Gray squares surrounding black-filled circles indicate rRT–PCR-positive specimens from which viral culture was unsuccessful. An asterisk indicates patients who required supplemental oxygen.