Respiratory failure and ARDS
An absolute majority of all critically ill COVID-19 patients present with severe respiratory insufficiency [8, 10,11,12, 15]. Sometimes clinical signs of dyspnea may be missing even in cases of severe hypoxia, especially in older patients . At least in the specific situation in Hubei, in China most severe oxygenation failures with an oxygenation index <100 mm Hg [8, 12] were already present when patients were admitted to ICU. Treatment with noninvasive ventilation or high-flow oxygen, as has become established for primary hypoxemic lung failure in the last few years, is critically discussed for COVID-19 treatment and many experts reject this approach [12, 22, 25]. Success rates in critically ill COVID-19-patients are limited, delayed intubation is associated with poor outcome and the treatment as well as a possibly necessary emergency intubation in cases of treatment failure increase the risk for transmission to staff [8, 12, 15, 22]; however, in situations with an imbalanced resources-needs ratio, this approach could help bridge the time until decision-making and intubation, or it could also be a therapeutic option in cases of lacking ventilatory capacities. For ARDS therapy, the commonly known intensive care principles apply, as e.g. documented in the S3 guidelines invasive ventilation. Classical rescue therapies for severe oxygenation failure, such as recruitment, relaxation and prone positioning are primarily successful in most patients [12, 15]. In the course of time some of the patients develop severe hypercapnia of unknown origin . Barotrauma, often observed in SARS, has been reported only in single cases; however, this might result from a trend towards more lung-protective ventilator settings compared to 2003 .
Whether or not patients benefit from extracorporeal membrane oxygenation (ECMO) therapy is not clear [15, 26]. If one basically assumes prognosis improvement with ECMO therapy in ARDS patients, then this should also apply for COVID-19 given the prominent pulmonary organ failure and the relative rarity of extrapulmonary organ failure. In a series of 28 cases, 14 had died, 5 were weaned and 9 were still under ECMO therapy at the time of manuscript submission . In the case of larger numbers of patients, a lack of ECMO treatment facilities is to be expected. Good patient selection and timely start are likely crucial for successful implementation.
In ICD-10-GM, COVID-19 was given the coding U07.1! as pathogen-specific secondary diagnosis code. Attention should be paid to correct coding.
Many antiviral and other agents are being used in patients, their application based on theoretical considerations, case studies and in vitro data about SARS and Middle East respiratory syndrome (MERS). Several clinical trials are being conducted. Most commonly used seem to be remdesivir, lopinavir/ritonavir (Kaletra®), also in combination with interferon beta 1b and chloroquine [27,28,29,30]; however, the current data situation does not allow concrete treatment recommendations for any of these substances. The substances’ pharmacokinetic interaction potential is not without problems (http://www.covid19-druginteractions.org/). The WHO as well as Chinese experts clearly advise against use of steroids because prolonged virus replication without clinical benefits was observed under steroid therapy in MERS [12, 25]. Delayed dramatic deterioration after initial improvement under protracted steroid application has been reported anecdotally for COVID-19 ; however, there is no consensus regarding benefit or harm of short-term steroid administration, and it is still being used .
Bacterial superinfections are reported, but they seem to occur less frequently than in influenza pneumonia. Empirical antibiotic therapy for community or nosocomially acquired pneumonia is recommended for all severely ill patients . As known for influenza, Aspergillus co-infections can occur as well .
Extrapulmonary organ failure
Shock is relatively rarely observed; in total, no more than up to one third of critically ill patients need catecholamine treatment [5, 8, 9, 11, 12, 15, 31, 32]; however, some patients die of refractory heart failure after some time in the course of disease, showing aspects of cardiogenic shock [10, 12]. It is not clear whether this results from a direct myocardial damage by infection, stress cardiomyopathy or right heart failure due to prolonged ARDS. Histological or echocardiographical findings have not been reported yet. Many patients suffer from kidney damage, around 20% need renal replacement therapy in the course of disease [8, 10,11,12]. As in all ICU patients, in cases of newly occurring shock with multiorgan failure there is strong suspicion of nosocomial infection with sepsis [8, 12].
Strategic considerations for referrals
Referring suspected cases or patients, especially if they are severely ill, to maximum care hospitals may seem to be an attractive strategy and is well-established practice in Germany for patients with severe, complex or rare medical conditions; however, such an approach would overburden maximum health care providers and would bring their functionality, e.g. as transregional trauma center, perinatal center, transplantation center and other highly specialized areas of care, to a halt. For this reason, community hospitals should provide intensive care for patients with COVID-19. Referral seems to only be sensible for few, well-selected patients with medical indications, e.g. for ECMO therapy.
Prognosis and sequelae of the disease
For COVID-19 patients treated on ICU, a mortality rate of 30–70% is expected [5, 8, 10, 11, 13, 15]. For older patients with ARDS, this is an entirely expectable estimation that is comparable to other severe pulmonary infections. In Hubei, the Chinese province that was initially most affected and where most of the data come from, access to intensive care treatment was delayed and the quality of care was probably reduced due to the exceptional situation. Thus, in one case series transfer to ICU took place a median of 1.5 days after onset of ARDS , in another case series some of the patients were treated on newly established ICUs , other authors report that only 25% of deceased patients were intubated and invasively ventilated at all . In survivors, usual consequences of long-term intensive care treatment have to be expected. For survivors of the SARS epidemic, a high rate of pulmonary fibrosis is reported . As there is also one case report with a newly emerged fibrosis in a COVID-19 patient , COVID-19 survivors should be followed-up closely.
Infobox Additional information in English